1,2-Dichloroethane → (S)-2-({(3S,8S)-7-((1R,3S)-3-tert. Butoxycarbonylamino-cyclopentanecarbonyl)-3-[4-(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

HRID 391950Notes

Reaction equation

HRID 391950 reaction equation
C(Cl)CCl.[C:5]([O:9][C:10]([NH:12][C@H:13]1[CH2:17][CH2:16][C@@H:15]([C:18]([OH:20])=O)[CH2:14]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].C[O:22][C:23](=[O:73])[C@@H:24]([NH:40][C:41]([C@@H:43]1[CH2:52][C:51]2[CH:50]=[C:49]3[O:53][CH2:54][C@H:55]([C:57]4[CH:62]=[CH:61][C:60]([O:63][CH2:64][C:65]5[CH:70]=[CH:69][C:68]([Cl:71])=[C:67]([Cl:72])[CH:66]=5)=[CH:59][CH:58]=4)[O:56][C:48]3=[CH:47][C:46]=2[CH2:45][NH:44]1)=[O:42])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([CH3:38])[C:33]=2[CH3:39])=[CH:28][CH:27]=1>C(Cl)Cl>[C:5]([O:9][C:10]([NH:12][C@H:13]1[CH2:17][CH2:16][C@@H:15]([C:18]([N:44]2[C@H:43]([C:41]([NH:40][C@@H:24]([CH2:25][C:26]3[CH:27]=[CH:28][C:29]([C:32]4[CH:37]=[CH:36][N:35]=[C:34]([CH3:38])[C:33]=4[CH3:39])=[CH:30][CH:31]=3)[C:23]([OH:73])=[O:22])=[O:42])[CH2:52][C:51]3[CH:50]=[C:49]4[O:53][CH2:54][C@H:55]([C:57]5[CH:62]=[CH:61][C:60]([O:63][CH2:64][C:65]6[CH:70]=[CH:69][C:68]([Cl:71])=[C:67]([Cl:72])[CH:66]=6)=[CH:59][CH:58]=5)[O:56][C:48]4=[CH:47][C:46]=3[CH2:45]2)=[O:20])[CH2:14]1)=[O:11])([CH3:6])([CH3:7])[CH3:8]

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 1512526(1R,3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acidHCID 58327416(S)-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)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester

Product 1

HCID 58327133(S)-2-({(3S,8S)-7-((1R,3S)-3-tert. Butoxycarbonylamino-cyclopentanecarbonyl)-3-[4-(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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

EDC (3 eq.) and (1R,3S)-3-tert-butoxycarbonylamino-cyclopentanecarboxylic acid (6 eq.) were dissolved in DCM and stirred for 40 minutes. To this solution was added (S)-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)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester (25 mg) and stirred for 12 hours. 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. LCMS (m/z): 950.

Workup

  1. stirringstirred for 12 hours
  2. 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-76b41c96a6da486e9baf16d5a135798a
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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