Methanesulfonyl chloride → (R)-7-cyano-2,3,4,5-tetrahydro-4-(phenylacetyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine
Reaction equation
CS(Cl)(=O)=O.Cl.Cl.Cl.N1C=C(C[N:15]2[C:21]3[CH:22]=CC(C4C=NC=CC=4)=[CH:25][C:20]=3[CH2:19][N:18]([C:32](=[O:37])[C:33](F)(F)F)[CH:17]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:16]2)N=C1>C(Cl)Cl.O>[C:16]([C:17]1[CH:38]=[CH:22][C:21]2[NH:15][CH2:16][C@@H:17]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:18]([C:32](=[O:37])[CH2:33][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:19][C:20]=2[CH:25]=1)#[N:15]Participants
5
Procedure
Methanesulfonyl chloride (3.68 mL, 47.6 mmol) was added dropwise as a solution in CH2Cl2 (20 mL) to a solution of Compound B (10 g, 36.6 mmol) in CH2Cl2 (130 mL) at 0° C. under argon. After stirring at rt for 16 hr the reaction was diluted with water (20 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×40 mL). The combined organic layers were washed with water (1×30 mL), KHSO4 (2×30 mL), water (1×30 mL), NaHCO3 (2×30 mL), brine (1×30 mL), dried over MgSO4, filtered and concentrated to afford a golden brown oil. The oil was crystalized from EtOAc/hexanes and the yellow solid triturated with hexane and dried to afford Compound C (10.6 g, 82 %). MS: [M+H]+ =351
Workup
- customThe layers were separated
- extractionthe aqueous layer was extracted with CH2Cl2 (2×40 mL)
- washThe combined organic layers were washed with water (1×30 mL), KHSO4 (2×30 mL), water (1×30 mL), NaHCO3 (2×30 mL), brine (1×30 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customto afford a golden brown oil
- customThe oil was crystalized from EtOAc/hexanes
- customthe yellow solid triturated with hexane
- customdried
Sources & evidence
- ORD record
- ord-5571878438d44c40b5575632e8f883a0
- Source dataset
- uspto-grants-2000_01
- Patent number
- US06011029
Reaction notes
Loading…