4,4-Difluoropiperidine-1-carbonyl chloride → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(4,4-difluoro-piperidine-1-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-yl)-phenyl]-propionic acid

HRID 391957Notes

Reaction equation

HRID 391957 reaction equation
C[O:2][C:3](=[O:53])[C@@H:4]([NH:20][C:21]([C@@H:23]1[CH2:32][C:31]2[CH:30]=[C:29]3[O:33][CH2:34][C@H:35]([C:37]4[CH:42]=[CH:41][C:40]([O:43][CH2:44][C:45]5[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=5)=[CH:39][CH:38]=4)[O:36][C:28]3=[CH:27][C:26]=2[CH2:25][NH:24]1)=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=2[CH3:19])=[CH:8][CH:7]=1.[F:54][C:55]1([F:64])[CH2:60][CH2:59][N:58]([C:61](Cl)=[O:62])[CH2:57][CH2:56]1>C(Cl)Cl>[Cl:52][C:47]1[CH:46]=[C:45]([CH:50]=[CH:49][C:48]=1[Cl:51])[CH2:44][O:43][C:40]1[CH:39]=[CH:38][C:37]([C@H:35]2[CH2:34][O:33][C:29]3=[CH:30][C:31]4[CH2:32][C@@H:23]([C:21]([NH:20][C@@H:4]([CH2:5][C:6]5[CH:11]=[CH:10][C:9]([C:12]6[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[C:13]=6[CH3:19])=[CH:8][CH:7]=5)[C:3]([OH:53])=[O:2])=[O:22])[N:24]([C:61]([N:58]5[CH2:59][CH2:60][C:55]([F:64])([F:54])[CH2:56][CH2:57]5)=[O:62])[CH2:25][C:26]=4[CH:27]=[C:28]3[O:36]2)=[CH:42][CH:41]=1

Participants

4

Reactant 2

HCID 552634244,4-Difluoropiperidine-1-carbonyl chlorideHCID 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 58327534(S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(4,4-difluoro-piperidine-1-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-yl)-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-yl)-phenyl]-propionic acid methyl ester (30 mg) in DCM (3 mL), 4,4-difluoro-piperidine-1-carbonyl chloride (5.0 eq, prepared according to General Procedure AD) according to General Procedure H and 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 mg). LCMS (m/z) 886.

Workup

  1. custompurified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+1% MeOH)

Sources & evidence

ORD record
ord-1c274c5083064ee8b1dbe56af89ab2b0
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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