4-Methylmorpholine → HCID 118287421, compound

HRID 526010Notes

Reaction equation

HRID 526010 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[CH2:5]([N:7]1[C:11]2=[N:12][C:13]([CH3:19])=[C:14]([C:16](O)=[O:17])[CH:15]=[C:10]2[CH:9]=[C:8]1[C:20](=[O:37])[NH:21][CH:22]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1)[C:23]([F:26])([F:25])[F:24])[CH3:6].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>[CH:1]1([NH:4][C:16]([C:14]2[CH:15]=[C:10]3[CH:9]=[C:8]([C:20]([NH:21][CH:22]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:35])([F:36])[F:34])[CH:28]=4)[C:23]([F:24])([F:25])[F:26])=[O:37])[N:7]([CH2:5][CH3:6])[C:11]3=[N:12][C:13]=2[CH3:19])=[O:17])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 69828CyclopropylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118275248HCID 118275248, compound

Product 1

HCID 118287421HCID 118287421, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Cyclopropylamine (0.0217 g, 0.380 mmol) was dissolved in N,N-dimethylformamide (2.3 ml) and 1-ethyl-6-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (0.150 g, 0.317 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (0.120 g, 0.317 mmol) and 4-methylmorpholine (0.105 ml, 0.951 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, dried over sodium sulphate, adsorbed on silica gel and chromatographed with cyclohexane/ethyl acetate (1:1). This gave 0.033 mg (18% of theory) of N5-cyclopropyl-1-ethyl-6-methyl-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-pyrrolo[2,3-b]pyridine-2,5-dicarboxamide. HPLC-MS: log P=3.52; mass (m/z): 513.1 (M+H)+; 1HNMR (D6-DMSO): δ 0.57 (m, 2H), 0.71 (m, 2H), 1.20 (t, 3H), 2.89 (s, 3H), 3.32 (s, 3H), 4.02 (q, 1H), 4.59 (q, 2H), 6.29-6.33 (m, 1H), 7.35 (s, 1H), 7.70-7.83 (m, 2H), 7.95 (s, 1H), 8.06 (m, 1H), 8.21 (s, 1H), 8.41 (d, 1H), 9.78 (d, 1H).

Workup

  1. extractionThe aqueous phase was extracted three times with ethyl acetate
  2. dry with materialdried over sodium sulphate
  3. customchromatographed with cyclohexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-58424e38742446d397cfd43faddf8a39
Source dataset
uspto-grants-2016_05
Patent number
US09345247B2

Reaction notes

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