2-Isopropyl-5-methyloxazole-4-carboxylic acid → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2-isopropyl-5-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 392000Notes

Reaction equation

HRID 392000 reaction equation
C[O:2][C:3](=[O:54])[C@@H:4]([NH:21][C:22]([C@@H:24]1[CH2:33][C:32]2[CH:31]=[C:30]3[O:34][CH2:35][C@H:36]([C:38]4[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]5[CH:51]=[CH:50][C:49]([Cl:52])=[C:48]([Cl:53])[CH:47]=5)=[CH:40][CH:39]=4)[O:37][C:29]3=[CH:28][C:27]=2[CH2:26][NH:25]1)=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[C:14]=2[CH3:20])=[CH:8][CH:7]=1.[CH:55]([C:58]1[O:59][C:60]([CH3:66])=[C:61]([C:63]([OH:65])=O)[N:62]=1)([CH3:57])[CH3:56]>C(Cl)Cl>[Cl:53][C:48]1[CH:47]=[C:46]([CH:51]=[CH:50][C:49]=1[Cl:52])[CH2:45][O:44][C:41]1[CH:42]=[CH:43][C:38]([C@H:36]2[CH2:35][O:34][C:30]3=[CH:31][C:32]4[CH2:33][C@@H:24]([C:22]([NH:21][C@@H:4]([CH2:5][C:6]5[CH:11]=[CH:10][C:9]([O:12][C:13]6[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[C:14]=6[CH3:20])=[CH:8][CH:7]=5)[C:3]([OH:54])=[O:2])=[O:23])[N:25]([C:63]([C:61]5[N:62]=[C:58]([CH:55]([CH3:56])[CH3:57])[O:59][C:60]=5[CH3:66])=[O:65])[CH2:26][C:27]=4[CH:28]=[C:29]3[O:37]2)=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 467377382-Isopropyl-5-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 58327264(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2-isopropyl-5-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

(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 (30 mg) was reacted with 2-isopropyl-5-methyl-oxazole-4-carboxylic acid (according to a procedure in Synthesis, Vol. 10, pp. 1569-71 (2005)) in DCM (3.0 mL) according to General Procedure A and directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound (8.5 mg). LCMS (m/z) 906.

Workup

  1. customaccording to a procedure in Synthesis, Vol. 10
  2. customdirectly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH)

Sources & evidence

ORD record
ord-d6f7459aa28547e599553e6c18cdb12d
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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