1,1'-Carbonyldiimidazole → (3R)-3-Cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanamide

HRID 1467451Notes

Reaction equation

HRID 1467451 reaction equation
[CH:1]1([C@H:6]([N:11]2[CH:15]=[C:14]([C:16]3[C:17]4[CH:24]=[CH:23][N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:18]=4[N:19]=[CH:20][N:21]=3)[CH:13]=[N:12]2)[CH2:7][C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1N=C[N:35](C(N2C=NC=C2)=O)C=1>CN(C=O)C>[CH:1]1([C@H:6]([N:11]2[CH:15]=[C:14]([C:16]3[C:17]4[CH:24]=[CH:23][N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[C:18]=4[N:19]=[CH:20][N:21]=3)[CH:13]=[N:12]2)[CH2:7][C:8]([NH2:35])=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 59420174(3R)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanoic acid

Product 1

HCID 59420147(3R)-3-Cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (3R)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanoic acid ((R)-23, 20 mg, 0.044 mmol) in DMF (1 mL) at room temperature was added N,N-carbonyldiimidazole (CDI, 21 mg, 0.13 mmol, 3.0 equiv). The reaction mixture was then stirred at room temperature and TLC was used to follow the reaction for formation of acyl imidazole (consumption of acid to a higher Rf spot with 30% EtOAc/hexane). When TLC showed that the acyl imidazole transformation was complete, ammonia gas was then bubbled through the stirred solution for 30 min to afford the amide (followed by LCMS). The excess amount of ammonia gas was evaporated by bubbling nitrogen vigorously through the solution. The crude product, (3R)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanamide ((R)-24), in DMF was used directly to the following reaction to convert amide ((R)-24) into the corresponding nitrile ((R)-20).

Workup

  1. customconsumption of acid to a higher Rf spot with 30% EtOAc/hexane)
  2. customammonia gas was then bubbled through the stirred solution for 30 min

Sources & evidence

ORD record
ord-17d1eb42bde0473e9a1d0b1df9e06051
Source dataset
uspto-grants-2015_04
Patent number
US09000161B2

Reaction notes

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