(R)-(+)-1-Phenylethyl isocyanate → (S)-3-(4'-Cyano-biphenyl-4-yl)-2-{[(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-((R)-1-phenyl-ethylcarbamoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-propionic acid

HRID 879874Notes

Reaction equation

HRID 879874 reaction equation
C[O:2][C:3](=[O:53])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][C:45]5[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=5)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][NH:24]1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[N:54]([C@@H:57]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[CH3:58])=[C:55]=[O:56]>>[C:18]([C:15]1[CH:14]=[CH:13][C:12]([C:9]2[CH:10]=[CH:11][C:6]([CH2:5][C@H:4]([NH:20][C:21]([C@@H:23]3[CH2:32][C:31]4[CH:30]=[C:29]5[O:33][CH2:34][C@H:35]([C:37]6[CH:38]=[CH:39][C:40]([O:43][CH2:44][C:45]7[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=7)=[CH:41][CH:42]=6)[O:36][C:28]5=[CH:27][C:26]=4[CH2:25][N:24]3[C:55](=[O:56])[NH:54][C@@H:57]([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)[CH3:58])=[O:22])[C:3]([OH:2])=[O:53])=[CH:7][CH:8]=2)=[CH:17][CH:16]=1)#[N:19]

Participants

3

Reactant 2

HCID 7018262(R)-(+)-1-Phenylethyl isocyanateHCID 58327184(S)-3-(4'-Cyano-biphenyl-4-yl)-2-({(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino)-propionic acid methyl ester

Product 1

HCID 58327556(S)-3-(4'-Cyano-biphenyl-4-yl)-2-{[(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-((R)-1-phenyl-ethylcarbamoyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-propionic acid

Procedure

To a solution of (S)-3-(4′-Cyano-biphenyl-4-yl)-2-({(3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino [2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester (20 mg) was added ((R)-1-isocyanato-ethyl)-benzene (5 equiv) and the reaction stirred at room temperature for 1 hour. The reaction mixture was directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH to 1:1 hexanes EtOAc+2% MeOH to 1:1 hexanes EtOAc+3% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound (26 mg). LCMS (m/z): 884.

Workup

  1. customThe reaction mixture was directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH to 1:1 hexanes EtOAc+2% MeOH to 1:1 hexanes EtOAc+3% MeOH)

Sources & evidence

ORD record
ord-8c4ceb5bcb1d49cfaa17d6c959c4796c
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

Loading…