3-Chlorophenylacetic acid → 3-{1-[(3-chlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amine

HRID 1909993Notes

Reaction equation

HRID 1909993 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[C:14]4[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=4[O:12][CH:11]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:22]=[C:23]([CH2:27][C:28](O)=[O:29])[CH:24]=[CH:25][CH:26]=1.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.CCOC(C)=O.O>[Cl:20][C:21]1[CH:22]=[C:23]([CH2:27][C:28]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]4[C:14]5[C:15]([NH2:19])=[N:16][CH:17]=[CH:18][C:13]=5[O:12][CH:11]=4)=[CH:7][CH:8]=3)[CH2:3][CH2:2]2)=[O:29])[CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 158793-Chlorophenylacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668234823-(2,3-dihydro-1H-indol-5-yl)furo[3,2-c]pyridin-4-amine

Product 1

HCID 668234873-{1-[(3-chlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amineYield 67.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(2,3-dihydro-1H-indol-5-yl)furo[3,2-c]pyridin-4-amine (150 mg, 0.440 mmol), 3-chlorophenylacetic acid (79 mg, 0.463 mmol), HATU (185 mg, 0.487 mmol), and Hunig's base (0.31 mL, 1.775 mmol) in N,N-Dimethylformamide (DMF) (3 mL) was stirred at room temperature for 4 days. Water (10 mL) was added, the mixture was stirred for about 4 hours, and the precipitate was collected by vacuum filtration. It was purified by flash chromatography (Analogix, 24 g SiO2, 25%-100% EtOAc in hexanes gradient over 30 minutes, then EtOAc for 10 minutes) to give 3-{1-[(3-chlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[3,2-c]pyridin-4-amine (126 mg, 0.296 mmol, 67.4% yield) as an off-white solid. LC/MS (ES) m/z=404, 406 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.25 (t, J=8.34 Hz, 2H), 3.93 (s, 2H), 4.25 (t, J=8.46 Hz, 2H), 5.54 (br. s., 2H), 6.93 (d, J=5.81 Hz, 1H), 7.24-7.46 (m, 6H), 7.86 (d, J=5.81 Hz, 1H), 7.92 (s, 1H), 8.16 (d, J=8.34 Hz, 1H).

Workup

  1. stirringthe mixture was stirred for about 4 hours
  2. filtrationthe precipitate was collected by vacuum filtration
  3. customIt was purified by flash chromatography (Analogix, 24 g SiO2, 25%-100% EtOAc in hexanes
  4. waitgradient over 30 minutes

Sources & evidence

ORD record
ord-ecd0d2e414a8404b8d97f4772c5b8921
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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