1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-cyclopropyl-ethyl)-amide

HRID 246135Notes

Reaction equation

HRID 246135 reaction equation
[CH:1]1([C@@H:4]([NH2:6])[CH3:5])[CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([C:12]([C:18]3[N:19]=[C:20]4[C:26]([C:27](O)=[O:28])=[CH:25][N:24]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:21]4=[N:22][CH:23]=3)=[N:13][N:14]2[CH3:17])=[CH:10][CH:9]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.ClCCl>[CH:1]1([C@@H:4]([NH:6][C:27]([C:26]2[C:20]3[C:21](=[N:22][CH:23]=[C:18]([C:12]4[C:11]5[C:15](=[CH:16][C:8]([Cl:7])=[CH:9][CH:10]=5)[N:14]([CH3:17])[N:13]=4)[N:19]=3)[N:24]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:25]=2)=[O:28])[CH3:5])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7363995(S)-1-CyclopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712883022-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-cyclopropyl-ethyl)-amide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-cyclopropylethanamine (32 mg, 0.373 mmol), 3 mL of dichloromethane, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (77 mg, 0.169 mmol), 4-dimethylaminopyridine (21 mg, 0.169 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (71 mg, 0.371 mmol) was stirred 18 h, then concentrated to an off-white solid. The solid was partitioned between 10 mL of ethyl acetate and 10 mL of a 10% citric acid solution. The organic layer was sequentially washed with 10 mL of water, 10 mL of a 10% NaOH solution, 10 mL of water, and 10 mL of a sat. aq. NaCl solution; dried over Na2SO4, filtered and concentrated to 70 mg (80%) of crude 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-cyclopropyl-ethyl)-amide, which was used without further purification. MS: (M+Na)+=547.

Workup

  1. concentrationconcentrated to an off-white solid
  2. customThe solid was partitioned between 10 mL of ethyl acetate and 10 mL of a 10% citric acid solution
  3. washThe organic layer was sequentially washed with 10 mL of water, 10 mL of a 10% NaOH solution, 10 mL of water, and 10 mL of a sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to 70 mg (80%) of crude 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-cyclopropyl-ethyl)-amide, which
  7. customwas used without further purification

Sources & evidence

ORD record
ord-fd4682ba849e45a09897f5632a2b7020
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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