Phosgene → 937731-95-8

HRID 603014Notes

Reaction equation

HRID 603014 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:19]2[CH2:22][CH:21]([C@@H:23]([C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([C:35]#[N:36])[CH:29]=3)[C:24]([F:27])([CH3:26])[CH3:25])[CH2:20]2)[C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([NH:14][NH2:15])=[O:13])=[CH:4][CH:3]=1.[C:37](Cl)(Cl)=[O:38]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([C:9]2[CH:18]=[CH:17][CH:16]=[C:11]([C:12]3[O:13][C:37](=[O:38])[NH:15][N:14]=3)[CH:10]=2)[N:19]2[CH2:22][CH:21]([C@@H:23]([C:28]3[CH:29]=[C:30]([CH:31]=[C:32]([F:34])[CH:33]=3)[C:35]#[N:36])[C:24]([F:27])([CH3:26])[CH3:25])[CH2:20]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6371PhosgeneHCID 67055368HCID 67055368, compound

Product 1

HCID 16745094937731-95-8

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3.0 g (5.85 mmol) of 3-((S)-(4-chlorophenyl){3-[(1S)-1-(3-cyano-5-fluorophenyl)-2-fluoro-2-methylpropyl]azetidin-1-yl}methyl)benzohydrazide in 100 mL of CH2Cl2 was added 3.73 mL (7.1 mmol) of phosgene solution (20% in toluene). The solution was stirred for 1.5 h at 0° C., The solution was concentrated ,and to the residue was added 6 mL of 2N NH3 in MeOH, and the mixture was concentrated again. The residue was purified by silica gel chromatography with CH2Cl2/acetone to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.26 (d, 3H, J1=22.1 Hz), 1.30 (d, 3H, J1=21.7 Hz), 2.39(t, 1H, J=8.0 Hz), 2.93-3.0(m, 2H), 3.12(t, 1H, J=7.3 Hz), 3.33(m, 1H), 3.69 (t, 1H, J=6.8 Hz), 4.35(s, 1H), 7.20 (d, 1H, J=9.7 Hz), 7.23 (d, 1H, J=7.3 Hz), 7.29-7.40(m, 7H), 7.48 (d, 1H, J=7.8 Hz), 7.68 (d, 1H, J=7.8 Hz), 7.97 (s, 1H); Mass Spectrum: m/e=535, (M+1, 35Cl), 537 (M+1, 37Cl).

Workup

  1. concentrationThe solution was concentrated ,and to the residue
  2. additionwas added 6 mL of 2N NH3 in MeOH
  3. concentrationthe mixture was concentrated again
  4. customThe residue was purified by silica gel chromatography with CH2Cl2/acetone

Sources & evidence

ORD record
ord-54b95ce3d42340da80bde2a1d93c0131
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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