Morpholine → HCID 58921245, compound

HRID 1365518Notes

Reaction equation

HRID 1365518 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:27][C:28]([NH:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:29])([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[NH:36]1CCOCC1.C[C:43]1(C)[C:69]2[C:64](=[C:65](P(C3C=CC=CC=3)C3C=CC=CC=3)[CH:66]=[CH:67][CH:68]=2)O[C:45]2[C:46](P(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:47][CH:48]=[CH:49][C:44]1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:31]1([NH:30][C:28]([NH:27][C:8]([C:5]2[CH:4]=[CH:3][C:2]([N:36]=[C:43]([C:69]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[CH:7][N:6]=2)([C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:29])[CH2:32][CH2:33][CH2:34][CH2:35]1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58921324HCID 58921324, compound

Product 1

HCID 58921245HCID 58921245, compoundYield 70.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1-(1-(5-Bromopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea (122 mg, 0.22 mmol), morpholine (1.3 eq), Pd2(dba)3 (70 mg), Xantphos (95 mg) and Na—O-t-Bu (84 mg) were stirred in toluene (0.7 mL) at room temperature. The reaction mixture was purged with N2 several times and then was heated at 100° C. for 2 h. The reaction mixture was cooled to room temperature, and CH2Cl2 was added. The resulting solution was filtered through Celite and concentrated to dryness. The residue was purified by chromatography (silica gel, hexanes/EtOAc) to give 1-cyclopentyl-3-(1-(5-(diphenylmethyleneamino)pyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea as white solids (101 mg, yield: 70.1%). LC-MS ESI 651.45 (M+H) (10-90% MeOH in H2O with 0.1% TFA in a 4-min run, retention time=4.47min).

Workup

  1. customThe reaction mixture was purged with N2 several times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionCH2Cl2 was added
  4. filtrationThe resulting solution was filtered through Celite
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-9f870adf52cf4120b1c7a655e02f3de7
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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