4-Methylmorpholine → HCID 90039588, compound

HRID 526008Notes

Reaction equation

HRID 526008 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].[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]2[CH:31]=[C:30]([C:32](O)=[O:33])[NH:29][C:25]2=[N:26][C:27]=1[CH3:28])=[O:21].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>[CH3:28][C:27]1[N:26]=[C:25]2[NH:29][C:30]([C:32](=[O:33])[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:31][C:24]2=[CH:23][C:22]=1[C:20]([O:19][CH3:18])=[O: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 90039786HCID 90039786, compound

Product 1

HCID 90039588HCID 90039588, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2,2,2-Trifluoro-1-[3-fluoro-3-(trifluoromethyl)phenyl]ethanamine (2.07 g, 8.54 mmol) was dissolved in N,N-dimethylformamide (6 ml), and 5-(methoxycarbonyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (1.60 g, 6.83 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (2.56 g, 6.83 mmol) and 4-methylmorpholine (2.53 ml, 20.50 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. This gave 1.74 g (55% of theory) of methyl 6-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate. HPLC-MS: log P=3.37; mass (m/z): 460.1 (M+H)+; 1H-NMR (D6-DMSO): δ 2.79 (s, 3H), 3.87 (s, 2H), 6.29-6.32 (m, 1H), 7.50 (s, 1H), 7.70-7.74 (m, 1H), 7.82-7.84 (m, 1H), 8.05 (d, 1H), 8.18 (s, 1H), 8.66 (m, 1H), 9.72-9.74 (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-4d0df455f9354ec1a2c7a725b3627ca4
Source dataset
uspto-grants-2016_05
Patent number
US09345247B2

Reaction notes

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