4-Methylmorpholine → HCID 86713974, compound

HRID 514252Notes

Reaction equation

HRID 514252 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[C:33](=[CH:34][C:35]=1[Cl:36])[NH:32][C:31]([C:37](O)=[O:38])=[CH:30]2)=[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.C(OCC)(=O)C.O>[Cl:36][C:35]1[CH:34]=[C:33]2[C:29]([CH:30]=[C:31]([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])[NH:32]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

8

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68293093HCID 68293093, compoundHCID 86713975HCID 86713975, compound

Product 1

HCID 86713974HCID 86713974, compoundYield 44.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,2,2-Trifluoro-1-[3-fluoro-3-(trifluoromethyl)phenyl]ethanamine (0.75 g, 3.08 mmol) was dissolved in N,N-dimethylformamide (52 ml), and 5-{[(tert-butoxycarbonyl)amino]methyl}-6-chloro-1H-indole-2-carboxylic acid (1.00 g, 3.08 mmol), N-[(1H-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate (1.17 g, 3.08 mmol) and 4-methylmorpholine (0.93 g, 9.24 mmol) were added. The reaction mixture was stirred at room temperature for 16 h and then water and ethyl acetate were added. After phase separation, the organic phase was washed with dilute sodium hydrogencarbonate solution and saturated sodium chloride solution and dried over sodium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (5/1). 0.75 g (40% of theory) of tert-butyl {[6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indol-5-yl]methyl}carbamate was obtained.

Workup

  1. customAfter phase separation
  2. washthe organic phase was washed with dilute sodium hydrogencarbonate solution and saturated sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was chromatographed with cyclohexane/ethyl acetate (5/1)

Sources & evidence

ORD record
ord-ce60fca31517453bbb6691468d4577a4
Source dataset
uspto-grants-2015_08
Patent number
US09107411B2

Reaction notes

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