Diisopropylethylamine → HCID 53476227, compound

HRID 245252Notes

Reaction equation

HRID 245252 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH2:18][N:19]3[CH2:24][CH2:23][CH:22]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)[CH2:21][CH2:20]3)=[C:16]([C:31]([OH:33])=O)[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([S:34]([CH3:37])(=[O:36])=[O:35])[CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:38][C:39]([F:49])([F:48])[C@H:40]([NH2:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(N(CC)C(C)C)(C)C.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>ClCCl.O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH2:18][N:19]3[CH2:24][CH2:23][CH:22]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[CH2:21][CH2:20]3)=[C:16]([C:31]([NH:47][C@H:40]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:39]([F:38])([F:48])[F:49])=[O:33])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([S:34]([CH3:37])(=[O:35])=[O:36])[CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 67384338HCID 67384338, compound

Product 1

HCID 53476227HCID 53476227, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-(3-bromophenyl)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-4-quinolinecarboxylic acid (0.250 g, 0.398 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.093 g, 0.438 mmol), and N,N-diisopropylethylamine (77 μL, 0.438 mmol) in dichloromethane (3.98 mL) was cooled to 0° C., and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane 2,4,6-trioxide (0.356 mL of 50% solution in ethyl acetate, 0.597 mmol) was added dropwise. The mixture was stirred at 0° C. for 2 h, warmed to room temperature, and stirred overnight. The mixture was diluted with water (2 mL) and saturated aqueous NaHCO3 (1 mL) was added. After stirring for 30 min, the organic phase was removed, passed over a phase separator, and concentrated in vacuo. The residue was dissolved in acetonitrile, and water was added slowly until the mixture became cloudy. The solid precipitate was collected by filtration, washed with water, and dried to afford 2-(3-bromophenyl)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.260 g, 88% yield). MS (m/z) 747.1 (M+H+).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred overnight
  3. additionwas added
  4. stirringAfter stirring for 30 min
  5. customthe organic phase was removed
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in acetonitrile
  8. additionwater was added slowly until the mixture
  9. filtrationThe solid precipitate was collected by filtration
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-0b22e99613ec4787960655964b9dcb7f
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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