Water → HCID 178523379, compound
Reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][CH2:16][C@H:15]([CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:14][CH2:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].O>CCOC(C)=O.CN(C=O)C>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([C@H:12]3[CH2:17][CH2:16][C@H:15]([CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:14][CH2:13]3)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1Participants
Procedure
To a suspension of benzyl [(trans-4-{[(3-chloropyrazin-2-yl)methyl]carbamoyl}cyclohexyl)methyl]carbamate (0.100 g, 0.220 mmol) in EtOAc (0.9 mL) and DMF (0.068 mL) at 0° C. was added slowly POCl3 (0.082 mL, 0.88 mmol). After stirring at rt for an hour, the mixture was cooled to 0° C. and solid NaHCO3 was added. After a further 10 min at 0° C. and 20 min at rt, the mixture was re-cooled to 0° C. and water (20 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the extracts washed with water (2×30 mL) and brine (30 mL) and then dried over Na2SO4 and concentrated in vacuo to afford 0.096 g of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.15-1.19 (m, 2H), 1.76-1.87 (m, 3H), 1.93-2.00 (m, 2H), 2.04-2.08 (m, 2H), 3.07 (m, 1H), 3.15 (t, J=6.4 Hz, 2H), 4.84 (br, 1H), 5.09 (s, 2H), 7.31-7.40 (m, 6H), 7.61 (d, J=4.8 Hz, 1H), 7.79 (s, 1H). MS (ES+): m/z 399.26 [MH+].
Workup
- temperaturethe mixture was cooled to 0° C.
- temperature20 min at rt, the mixture was re-cooled to 0° C.
- extractionThe reaction mixture was extracted with EtOAc (3×20 mL)
- washthe extracts washed with water (2×30 mL) and brine (30 mL)
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-6a0fe53c2b8b4b4687de2d374b05ca20
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07651687B2
Reaction notes
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