2-Pyridinecarboxaldehyde → (S)-2-({(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-pyridin-2-ylmethyl-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 391929Notes

Reaction equation

HRID 391929 reaction equation
C[O:2][C:3](=O)[C@@H:4]([NH:32][C:33](OC(C)(C)C)=O)[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25](Cl)=[C:24](Cl)[CH:23]=4)=[CH:16][CH:15]=3)[CH2:12][O:13][C:8]=2[CH:7]=1.[ClH:41].[ClH:42].C[O:44][C:45](=[O:63])[C@@H:46]([NH2:62])[CH2:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][N:57]=[C:56]([CH3:60])[C:55]=2[CH3:61])=[CH:50][CH:49]=1.[N:64]1[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[CH:70]=O>>[Cl:41][C:26]1[CH:27]=[C:22]([CH:23]=[CH:24][C:25]=1[Cl:42])[CH2:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([C@H:11]2[CH2:12][O:13][C:8]3=[CH:7][C:6]4[CH2:5][C@@H:4]([C:3]([NH:62][C@@H:46]([CH2:47][C:48]5[CH:53]=[CH:52][C:51]([C:54]6[CH:59]=[CH:58][N:57]=[C:56]([CH3:60])[C:55]=6[CH3:61])=[CH:50][CH:49]=5)[C:45]([OH:44])=[O:63])=[O:2])[N:32]([CH2:70][C:65]5[CH:66]=[CH:67][CH:68]=[CH:69][N:64]=5)[CH2:33][C:31]=4[CH:30]=[C:9]3[O:10]2)=[CH:19][CH:18]=1

Participants

4

Reactant 3

HCID 142732-PyridinecarboxaldehydeHCID 58327295(S)-2-tert-Butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-propionic acid methyl esterHCID 66719267L-Phenylalanine, 4-(2,3-dimethyl-4-pyridinyl)-, methyl ester, hydrochloride (1:2)

Product 1

HCID 58327403(S)-2-({(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-pyridin-2-ylmethyl-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

Procedure

The title compound (13 mg) was prepared from (S)-2-tert-butoxycarbonylamino-3-{(S)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-propionic acid methyl ester, which was deprotected according to General Procedure C, subjected to General Procedure V, then reprotected. Hydrolysis followed General Procedure B and the resulting acid and (S)-2-amino-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester dihydrochloride were reacted according to General Procedures L and C. The amine was treated with 2-pyridinecarboxaldehyde, then hydrolyzed according to General Procedures D and B. LCMS (m/z): 830.

Workup

  1. customHydrolysis

Sources & evidence

ORD record
ord-7e9026b4138340a9a1a30882c214e181
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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