Chlorophenyl isocyanate → HCID 6540299, compound

HRID 749109Notes

Reaction equation

HRID 749109 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C@@H:17]([CH3:22])[C:18]([CH3:21])([OH:20])[CH3:19])[N:11]=2)=[CH:5][CH:4]=1.[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[N:30]=[C:31]=[O:32]>ClC(Cl)C.C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[NH:30][C:31](=[O:32])[N:9]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C@@H:17]([CH3:22])[C:18]([OH:20])([CH3:21])[CH3:19])[N:11]=1)[C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1

Participants

5

Reactant 2

HCID 76833Chlorophenyl isocyanateHCID 59751987HCID 59751987, compound

Product 1

HCID 6540299HCID 6540299, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (3S)-3-[4-(4-methoxy-phenylamino)pyrimidin-2-ylamino]-2-methyl-butan-2-ol, 2, (129 mg, 0.427 mmol) in dichloroethane (3 mL) is added 2-chlorophenyl isocyanate (57 μL, 0.469 mmol) dropwise via syringe. The reaction is stirred at room temperature for 2 hours. Additional 2-chloroisocyanate (57 μL, 0.469 mmol) is added and the reaction mixture stirred at room temperature for 16 hours after which the reaction mixture is diluted with CH2Cl2 (30 mL), and washed with saturated aqueous sodium bicarbonate solution (20 mL). The aqueous layer is extracted with CH2Cl2 (20 mL) and the combined organic layers washed with water and brine and dried over sodium sulfate, filtered and concentrated in vacuo to afford a crude residue which is purified over silica (5% to 20% Et2O/CH2Cl2 to 10% MeOH/CH2Cl2) to afford the desired product as a white solid. 1H NMR (300 MHz, CDCl3) δ 13.04 (br s, 1H), 8.41 (d, J=8.0 Hz, 1H), 7.92 (d, J=6.0 Hz, 1H), 7.37-7.16 (m, 4H), 7.17 (d, J=8.9 Hz, 2H), 7.02 (d, J=8.9 Hz, 2H), 5.56 (m, 2H), 4.05 (m, 1H), 3.85 (s, 3H), 1.30 (s, 3H), 1.25 (d, J=6.9 Hz, 3H), 1.23 (s, 3H); MS (ESI) m/z 456 (M+1).

Workup

  1. stirringthe reaction mixture stirred at room temperature for 16 hours after which the reaction mixture
  2. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
  3. extractionThe aqueous layer is extracted with CH2Cl2 (20 mL)
  4. washthe combined organic layers washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a crude residue which
  9. customis purified over silica (5% to 20% Et2O/CH2Cl2 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1a69489a75404058a871da3c0c51e44e
Source dataset
uspto-grants-2008_07
Patent number
US07402589B2

Reaction notes

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