Diisopropylethylamine → 3-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amine

HRID 1910089Notes

Reaction equation

HRID 1910089 reaction equation
[F:1][C:2]1[C:10]([C:11]2[C:15]3[C:16]([NH2:20])=[N:17][CH:18]=[CH:19][C:14]=3[O:13][CH:12]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][NH:6]2.[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[CH2:29][C:30](O)=[O:31].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)C=O>[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[CH2:29][C:30]([N:6]1[C:7]2[C:3](=[C:2]([F:1])[C:10]([C:11]3[C:15]4[C:16]([NH2:20])=[N:17][CH:18]=[CH:19][C:14]=4[O:13][CH:12]=3)=[CH:9][CH:8]=2)[CH2:4][CH2:5]1)=[O:31]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5228232,5-Difluorophenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668240273-(4-fluoro-2,3-dihydro-1H-indol-5-yl)furo[3,2-c]pyridin-4-amine

Product 1

HCID 668236753-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amineYield 84.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(4-fluoro-2,3-dihydro-1H-indol-5-yl)furo[3,2-c]pyridin-4-amine (190 mg, 0.555 mmol), 2,5-difluorophenylacetic acid (100 mg, 0.583 mmol), HATU (232 mg, 0.611 mmol), and Hunig's base (0.388 mL, 2.221 mmol) in N,N-Dimethylformamide (DMF) (5 mL) was stirred at room temperature for 2 hours. HPLC indicated complete consumption of starting material, so the mixture was poured into water (30 mL), the suspension was stirred for a few minutes, and the precipitate was collected by vacuum filtration and dried in the vacuum oven overnight to give 3-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amine (209 mg, 0.469 mmol, 84% yield) as a light tan solid. LC/MS (ES) m/z=424 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.26-3.31 (d, J=8.34 Hz, 2H), 3.97 (s, 3H), 4.38 (t, J=8.46 Hz, 2H), 5.48 (s, 2H), 6.95 (d, J=5.81 Hz, 1H), 7.14-7.35 (m, 4H), 7.87 (d, J=6.06 Hz, 1H), 7.93 (d, J=8.08 Hz, 1H), 7.96 (s, 1H).

Workup

  1. customconsumption of starting material
  2. additionso the mixture was poured into water (30 mL)
  3. stirringthe suspension was stirred for a few minutes
  4. filtrationthe precipitate was collected by vacuum filtration
  5. customdried in the vacuum oven overnight

Sources & evidence

ORD record
ord-1a1a2187108642ccbcf12a5c3b7f0431
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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