Diisopropylethylamine → tert-butyl 2-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-2-methylpropanoate

HRID 246578Notes

Reaction equation

HRID 246578 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Cl.[NH2:25][C:26]([CH3:35])([CH3:34])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:25][C:26]([CH3:35])([CH3:34])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12186776Tert-butyl 2-amino-2-methylpropanoate hydrochlorideHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71280209tert-butyl 2-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-2-methylpropanoateYield 51.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.323 mmol), tert-butyl 2-amino-2-methylpropanoate hydrochloride (82 mg, 0.42 mmol), HATU (160 mmol, 0.42 mmol) and DIPEA (66 mg, 0.51 mmol) in 6 mL of DMF was stirred at room temperature for 16 hours. The solvent was evaporated at 70° C. under reduced pressure and the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (1:1, v/v) to give tert-butyl 2-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-2-methylpropanoate (75 mg, 51.8%) as a white solid. MS: (M+H)+=453; 1H NMR (300 MHz, DMSO): δ 13.93 (s, 1H), 9.13 (s, 1H), 8.57-8.52 (m, 1H), 8.48 (s, 1H), 8.30 (s, 1H), 7.72 (dd, 1H, J=9.8, 2.1 Hz), 7.21-7.15 (m, 1H), 4.18 (s, 3H), 1.63 (s, 6H), 1.25 (s, 9H).

Workup

  1. customThe solvent was evaporated at 70° C. under reduced pressure
  2. customthe residue was purified by column chromatography (silica gel, 200-300 mesh
  3. washeluting with a mixture of petroleum ether and ethyl acetate (1:1

Sources & evidence

ORD record
ord-5f13d4b1f4ef4781a182e9c8b0e59c84
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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