4-Methylmorpholine → HCID 131735593, compound

HRID 526016Notes

Reaction equation

HRID 526016 reaction equation
[F:1][C:2]([F:17])([F:16])[CH:3]([C:5]1[CH2:6][C:7](F)([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:9][CH:10]=1)[NH2:4].[C:18]([O:22][C:23]([NH:25][CH2:26][C:27]1[CH:28]=[C:29]2[CH:36]=[C:35]([C:37](O)=[O:38])[NH:34][C:30]2=[N:31][C:32]=1[CH3:33])=[O:24])([CH3:21])([CH3:20])[CH3:19].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O.O>[CH3:33][C:32]1[N:31]=[C:30]2[NH:34][C:35]([C:37](=[O:38])[NH:4][CH:3]([C:5]3[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=3)[C:2]([F:17])([F:16])[F:1])=[CH:36][C:29]2=[CH:28][C:27]=1[CH2:26][NH:25][C:23](=[O:24])[O:22][C:18]([CH3:20])([CH3:19])[CH3:21]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86713975HCID 86713975, compoundHCID 118275230HCID 118275230, compound

Product 1

HCID 131735593HCID 131735593, compoundYield 33.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2,2,2-Trifluoro-1-[3-fluoro-3-(trifluoromethyl)phenyl]ethanamine (726 mg, 2.98 mmol) was dissolved in N,N-dimethylformamide (10 ml), and 5-{[(tert-butoxycarbonyl)amino]methyl}-6-methyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (730 g, 2.39 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (907 mg, 2.39 mmol) and 4-methylmorpholine (725 mg, 7.17 mmol) were added. The reaction mixture was stirred at room temperature for 16 h and then water was added. The aqueous phase was extracted three times with ethyl acetate and the extract was dried over sodium sulphate, adsorbed on silica gel and chromatographed with ethyl acetate. 420 mg (33% of theory) of tert-butyl {[6-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}carbamate were obtained. HPLC-MS: log P=3.49; mass (m/z): 531.2 (M+H)+; 1HNMR (D6-DMSO): δ 1.40 (s, 9H), 3.30 (s, 3H), 4.20 (m, 2H), 6.29-6.32 (m, 1H), 7.35 (s, 1H), 7.71 (m, 1H), 7.82-7.84 (m, 1H), 8.03 (d, 1H), 8.17 (s, 1H), 9.43 (m, 1H).

Workup

  1. extractionThe aqueous phase was extracted three times with ethyl acetate
  2. dry with materialthe extract was dried over sodium sulphate
  3. customchromatographed with ethyl acetate

Sources & evidence

ORD record
ord-ace6219057724ff192288ee44f5d5584
Source dataset
uspto-grants-2016_05
Patent number
US09345247B2

Reaction notes

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