1,2-Dichloroethane → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2-methyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

HRID 391962Notes

Reaction equation

HRID 391962 reaction equation
C(Cl)CCl.[CH3:5][C:6]1[O:7][CH:8]=[C:9]([C:11]([OH:13])=O)[N:10]=1.C[O:15][C:16](=[O:67])[C@@H:17]([NH:34][C:35]([C@@H:37]1[CH2:46][C:45]2[CH:44]=[C:43]3[O:47][CH2:48][C@H:49]([C:51]4[CH:56]=[CH:55][C:54]([O:57][CH2:58][C:59]5[CH:64]=[CH:63][C:62]([Cl:65])=[C:61]([Cl:66])[CH:60]=5)=[CH:53][CH:52]=4)[O:50][C:42]3=[CH:41][C:40]=2[CH2:39][NH:38]1)=[O:36])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[C:27]=2[CH3:33])=[CH:21][CH:20]=1>C(Cl)Cl>[Cl:66][C:61]1[CH:60]=[C:59]([CH:64]=[CH:63][C:62]=1[Cl:65])[CH2:58][O:57][C:54]1[CH:55]=[CH:56][C:51]([C@H:49]2[CH2:48][O:47][C:43]3=[CH:44][C:45]4[CH2:46][C@@H:37]([C:35]([NH:34][C@@H:17]([CH2:18][C:19]5[CH:24]=[CH:23][C:22]([O:25][C:26]6[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[C:27]=6[CH3:33])=[CH:21][CH:20]=5)[C:16]([OH:67])=[O:15])=[O:36])[N:38]([C:11]([C:9]5[N:10]=[C:6]([CH3:5])[O:7][CH:8]=5)=[O:13])[CH2:39][C:40]=4[CH:41]=[C:42]3[O:50]2)=[CH:52][CH:53]=1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 5394042-Methyloxazole-4-carboxylic acidHCID 58327121(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-yloxy)-phenyl]-propionic acid methyl ester

Product 1

HCID 58327449(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2-methyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

EDC (5 eq.) and 2-methyl-oxazole-4-carboxylic acid (10 equiv) were dissolved in DCM and stirred 40 min. 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-yloxy)-phenyl]-propionic acid methyl ester and stirred for 12 h. 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 (12 mg). LCMS (m/z): 866.

Workup

  1. stirringstirred for 12 h
  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-4400bccc67a944a28e172318c3b31950
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

Loading…