Morpholine → HCID 58920259, compound

HRID 1365515Notes

Reaction equation

HRID 1365515 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]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=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:16]2[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=2)([C:5]2[CH:4]=[CH:3][C:2]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:7][N:6]=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 58920259HCID 58920259, compoundYield 60.9%

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 (64 mg, 0. 12 mmol), morpholine (1.3 eq), Pd2(dba)3 (0.2 eq), Xantphos (0.6 eq) and Na—O-t-Bu (3.2 eq) were stirred in toluene (0.5 mL) at room temperature. The reaction mixture was purged with N2 several times and then was heated at 100° C. for 3.5 h. The reaction mixture was cooled to room temperature, and Et2O was added. The resulting solution was washed with H2O, brine, dried (MgSO4), filtered, and concentrated to dryness. The residue was purified by chromatography (silica gel, hexanes/EtOAc) to give 1-cyclopentyl-3-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-(5-morpholinopyridin-2-yl)-2-phenylethyl)urea (39 mg, yield: 60.9%). LC-MS ESI 557.28 (M+H) (10-90% MeOH in H2O with 0.1% TFA in a 4-min run, retention time=3.63 min); 1H NMR (400 MHz, CDCl3) δ ppm 7.94 (d, J=2.9 Hz, 1 H), 7.57 (s, 1 H), 7.40 (d, J=10.0 Hz, 1 H), 7.28 (s, 1 H), 7.24-7.17 (m, 2 H), 7.14 (d, J=7.3 Hz, 1 H), 7.09 (t, J=7.5 Hz, 2 H), 7.02 (d, J=8.8 Hz, 1 H), 6.66 (d, J=7.6 Hz, 2 H), 4.48 (d, J=12.5 Hz, 1 H), 4.34 (d, J=7.1 Hz, 1 H), 4.00-3.91 (m, 1 H), 3.90-3.87 (m, 4 H), 3.56 (d, J=12.5 Hz, 1 H), 3.18 (m, 4 H), 2.09-2.01 (m, 1 H), 1.92-1.83 (m, 1 H), 1.68-1.57(m, 4 H), 1.49-1.40 (m, 1H), 1.32-1.24 (m, 1 H).

Workup

  1. customThe reaction mixture was purged with N2 several times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionEt2O was added
  4. washThe resulting solution was washed with H2O, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-36e4455413844fd8b0a95d1c8fcab4f2
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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