4-(Difluoromethoxy)benzylamine → HCID 178515696, compound

HRID 1023184Notes

Reaction equation

HRID 1023184 reaction equation
Br[C:2]1[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[CH2:13][CH2:12]3)[O:4][N:3]=1.[F:20][CH:21]([F:31])[O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH2:30])=[CH:25][CH:24]=1>CO>[F:20][CH:21]([F:31])[O:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][NH:30][C:2]2[CH2:6][CH:5]([CH2:7][O:8][C:9]3[CH:10]=[C:11]4[C:16](=[CH:17][CH:18]=3)[NH:15][C:14](=[O:19])[CH2:13][CH2:12]4)[O:4][N:3]=2)=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 20633524-(Difluoromethoxy)benzylamineHCID 866804266-((3-bromo-4,5-dihydroisoxazol-5-yl)methoxy)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 178515696HCID 178515696, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-((3-bromo-4,5-dihydroisoxazol-5-yl)methoxy)-3,4-dihydroquinolin-2(1H)-one (0.1 g, 0.308 mmol) and (4-(difluoromethoxy)phenyl)methanamine (0.149 g, 0.923 mmol) were heated at 160° C. for 30 min. The reaction mixture was dissolved in methanol, concentrated, and the crude product purified by preparative HPLC on a Kromasil C4 column (250×20 mm) using a 0-100% gradient of ACN in 0.1% TFA to give 6-((3-(4-(difluoromethoxy)benzylamino)-4,5-dihydroisoxazol-5-yl)methoxy)-3,4-dihydroquinolin-2(1H)-one as a white solid (0.015 g, 23%). 1H NMR 400 MHz, DMSO-d6: δ 2.41 (q, J=7.20 Hz, 2H), 2.78-2.85 (m, 3H), 3.08 (q, J=9.60 Hz, 1H), 3.89-3.97 (m, 2H), 4.18 (d, J=6.00 Hz, 2H), 4.62-4.65 (m, 1H), 6.62 (t, J=6.00 Hz, 1H), 6.72-6.78 (m, 2H), 6.81 (d, J=2.00 Hz, 1H), 7.02-7.39 (m, 5H), 9.91 (s, 1H). LCMS: RT 1.501 min; LCMS (ES-API), m/z 418.2 (M+H).

Workup

  1. concentrationconcentrated
  2. customthe crude product purified by preparative HPLC on a Kromasil C4 column (250×20 mm)

Sources & evidence

ORD record
ord-7d61a071facf442d8e1da040066b9386
Source dataset
uspto-grants-2014_05
Patent number
US08722670B2

Reaction notes

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