Formic Acid → Bms-911543

HRID 220388Notes

Reaction equation

HRID 220388 reaction equation
[CH:1]1([N:4]([CH:30]2[CH2:32][CH2:31]2)[C:5]([C:7]2[N:27]([CH2:28][CH3:29])[C:10]3=[N:11][C:12]([NH:19]/[C:20](/SC)=[CH:21]/[C:22](=O)[CH3:23])=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:33][N:34](C(OCCCC)=O)[NH2:35].C(O)=O>C(O)(=O)C>[CH:1]1([N:4]([CH:30]2[CH2:31][CH2:32]2)[C:5]([C:7]2[N:27]([CH2:28][CH3:29])[C:10]3=[N:11][C:12]([NH:19][C:20]4[CH:21]=[C:22]([CH3:23])[N:34]([CH3:33])[N:35]=4)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 284Formic AcidHCID 20464644HCID 20464644, compoundHCID 58180553(Z)-N,N-dicyclopropyl-6-ethyl-1-methyl-4-(1-(methylthio)-3-oxobut-1-enylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 50922691Bms-911543Yield 67.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of (Z)-N,N-dicyclopropyl-6-ethyl-1-methyl-4-(1-(methylthio)-3-oxobut-1-enylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 72B, 70 mg, 0.155 mmol) and tent-butyl 1-methylhydrazinecarboxylate (0.046 mL, 0.309 mmol) in acetic acid (1 mL) wan stirred at 35° C. for 4 h (monitored by LC/MS until no starting material left). Formic acid (0.5 mL) was added and stirred at 60° C. for 6 h. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column, eluting with 2-10% methanol/dichloromethane). The impure product was further purified by preparative HPLC to give N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (45 mg, 63.9% yield) as an off-white solid.

Workup

  1. waitleft)
  2. stirringstirred at 60° C. for 6 h
  3. customSolvent was evaporated
  4. customthe crude product was purified by flash chromatography on silica gel using
  5. washan automated ISCO system (12 g column, eluting with 2-10% methanol/dichloromethane)
  6. customThe impure product was further purified by preparative HPLC

Sources & evidence

ORD record
ord-a5e7a986abe24756b93081c3e1b5a10c
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

Loading…