Methanol → (S)-2-{[(3S,8S)-3-[3-(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}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid

HRID 391980Notes

Reaction equation

HRID 391980 reaction equation
[CH3:1][C@@H:2]([N:9]=[C:10]=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[O:13][C:14](=[O:64])[C@@H:15]([NH:31][C:32]([C@@H:34]1[CH2:43][C:42]2[CH:41]=[C:40]3[O:44][CH2:45][C@H:46]([C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([O:54][CH2:55][C:56]5[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([Cl:63])[CH:57]=5)[CH:49]=4)[O:47][C:39]3=[CH:38][C:37]=2[CH2:36][NH:35]1)=[O:33])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[C:24]=2[CH3:30])=[CH:19][CH:18]=1.CO>C(Cl)Cl>[Cl:63][C:58]1[CH:57]=[C:56]([CH:61]=[CH:60][C:59]=1[Cl:62])[CH2:55][O:54][C:50]1[CH:49]=[C:48]([C@H:46]2[CH2:45][O:44][C:40]3=[CH:41][C:42]4[CH2:43][C@@H:34]([C:32]([NH:31][C@@H:15]([CH2:16][C:17]5[CH:22]=[CH:21][C:20]([C:23]6[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[C:24]=6[CH3:30])=[CH:19][CH:18]=5)[C:14]([OH:64])=[O:13])=[O:33])[N:35]([C:10](=[O:11])[NH:9][C@@H:2]([C:3]5[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=5)[CH3:1])[CH2:36][C:37]=4[CH:38]=[C:39]3[O:47]2)[CH:53]=[CH:52][CH:51]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 7018262(R)-(+)-1-Phenylethyl isocyanateHCID 58327094(S)-2-({(3S,8S)-3-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester

Product 1

HCID 58327110(S)-2-{[(3S,8S)-3-[3-(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}-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acidYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-(+)-α-Methylbenzyl isocyanate (5 mg) was added to a solution of (S)-2-({(3S,8S)-3-[3-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (20 mg) in 0.5 mL DCM and stirred for 1 h at room temperature. The reaction mixture was directly loaded onto a silica gel column (1:1 EtOAc/hexanes to 6% MeOH in 1:1 EtOAc/hexanes) to isolate the desired product (16 mg).

Sources & evidence

ORD record
ord-eb4f10b1510a4f52ba4e73871543fba4
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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