WO2010016005 Substituted 2-heterocyclyamino pyrazine compounds as CHK-1 inhibitors
Scaffold: Amino pyrazine
| Steps | Conditions | Reactions |
| a | Diethyl carbonate / NaH / Dioxane | Ester synthesis (Nucleophilic substitution) |
| b |
1. TFA 2. CBz-Cl / DCM |
Boc Deprotection / CBz Protection |
| c |
HSCH2CH2SH / lnCl3 |
Ketone protection |
| d |
NaOH aq / MeOH |
Carboxylic acid synthesis (Ester hydrolysis) |
| e |
DPPA / Et3N / t-BuOH |
Carbamate synthesis (Curtius rearrangement) |
| f |
HF / pyridine / DCM |
Fluorination |
| g | TFA / DCM | Boc deprotection |
| Steps | Conditions | Reactions |
| a | CBz-Cl / Et3N / DCM | CBz protection |
| b | MsCl / Et3N | Mesyl synthesis |
| c | Et3N | Alkene synthesis |
| d | m-CPBA / DCM | Epoxide synthesis |
| e | Et3N.3HF | Fluorination |
| f | MsCl / Et3N / DCM | Mesyl synthesis |
| g | NaN3 / DMF | Azido synthesis |
| h | PPh3 / H2O / THF | Primary amine synthesis (Staudinger reaction) |
| Steps | Conditions | Reactions |
| a | DIAD / PPh3 / p-nitrobenzoic acid / THF | Ester synthesis (Mitsunobu reaction) |
| b | LiOH aq / THF | Hydroxyl synthesis (Ester hydrolysis) |
| c | MsCl / Et3N / DCM | Mesyl synthesis |
| d | NaN3 / DMF | Azido synthesis |
| e | PPh3 / H2O / THF | Primary amine synthesis (Staudinger reaction) |
| Steps | Conditions | Reactions |
| a |
1. ammonia / EtOH 2. Boc2O / DCM |
Epoxide opening / Boc protection |
| b | Separation | Chiral separation |
| c | MeI / NaH / THF | Methoxy synthesis |
| d | HCl / Dioxane | Boc deprotection |
| Steps | Conditions | Reactions |
| a |
MsCl / DCM |
Mesyl synthesis |
| b | Zn / NaI / DME | Methoxy deprotection |
| c | H2 / Pd-C / MeOH | Cbz deprotection |
| Steps | Conditions | Reactions |
| a | MsCl / Et3N / DCM | Mesyl synthesis |
| b | TBAF / THF | Fluorination |
| c | AcOH / THF / H2O | THP deprotection |
| d | MsCl / Et3N / DCM | Mesyl synthesis |
| e | NaN3 / DMF | Azido synthesis |
| f | PPh3 / H2O / THF | Primary amine synthesis (Staudinger reaction) |
| Steps | Conditions | Reactions |
| a | Et3N / NMP | Secondary amine synthesis (Nucleophilic substitution) |
| b | Cs2CO3 / DMF | Tertiary amine synthesis (Nucleophilic substitution) |
| c | HCl / Dioxane | Boc deprotection |
| Steps | Conditions | Reactions |
| a | (CH3)2CH-MgCl / nBu3SnCl / THF | Tributyltin synthesis |
| b | Pd(PPh3)4 / Xylene | Stille coupling |
| Steps | Conditions | Reactions |
| a | Pd(AcO)2 / PPh3 / K2CO3 / dioxane | Heck reaction |
| b | CsF / DMSO | Secondary amine synthesis (nucleophilic substitution) |
| Steps | Conditions | Reactions |
| a | Pd(dba)3 / BINAP / Cs2CO3 / Toluene | Buchwald-Hartwig amination |
| Steps | Conditions | Reactions |
| a | Pd(dba)3 / BippyPhos / Cs2CO3 / MeOH | Buchwald-Hartwig reaction |
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