4-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)(cyano)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamide

HRID 1476352Notes

Reaction equation

HRID 1476352 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C@H:15]([C:31]#[N:32])[CH:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)=[CH:5][CH:4]=1.[O:33]1[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][C@@H:41]([NH:50][C:51]2[CH:56]=[CH:55][C:54]([S:57]([NH2:60])(=[O:59])=[O:58])=[CH:53][C:52]=2[S:61]([C:64]([F:67])([F:66])[F:65])(=[O:63])=[O:62])[CH2:42][S:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:35][CH2:34]1>>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C@H:15]([C:31]#[N:32])[CH:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[CH:24][C:25]([C:26]([NH:60][S:57]([C:54]4[CH:55]=[CH:56][C:51]([NH:50][C@H:41]([CH2:40][CH2:39][N:36]5[CH2:37][CH2:38][O:33][CH2:34][CH2:35]5)[CH2:42][S:43][C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=5)=[C:52]([S:61]([C:64]([F:67])([F:65])[F:66])(=[O:63])=[O:62])[CH:53]=4)(=[O:58])=[O:59])=[O:27])=[CH:29][CH:30]=3)[CH2:18][CH2:17]2)=[CH:7][CH:8]=1

Participants

3

Reactant 2

HCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide2×HCID 131732789(R)-4-(4-((4'-Chlorobiphenyl-2-yl)(cyano)methyl)piperidin-1-yl)benzoic acid, hydrochloride salt2×

Product 1

HCID 866618944-(4-((R)-(4'-chlorobiphenyl-2-yl)(cyano)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonyl)benzamideYield 20.5%

Procedure

The title product (19.8 mg, yield: 20%) was prepared using a procedure similar to the one described for the synthesis of EXAMPLE 14. (R)-4-(4-((4′-Chlorobiphenyl-2-yl)(cyano)methyl)piperidin-1-yl)benzoic acid, hydrochloride salt (INTERMEDIATE 84, 44.9 mg, 0.1 mmol) and (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 54.4 mg, 0.1 mmol) were used as starting materials. The resulting product was purified by column chromatography (ISCO, 4 g silica gel column, eluting with 0→5% MeOH/DCM) followed by further purification by column chromatography (ISCO, 4 g silica gel column, eluting first with 0→100% EtOAc/hexanes and then with 0→5% MeOH/DCM), providing the title product.

Workup

  1. customdescribed for the synthesis of EXAMPLE 14
  2. customThe resulting product was purified by column chromatography (ISCO, 4 g silica gel column, eluting with 0→5% MeOH/DCM)
  3. customfollowed by further purification by column chromatography (ISCO, 4 g silica gel column
  4. washeluting first with 0→100% EtOAc/hexanes
  5. customwith 0→5% MeOH/DCM), providing the title product

Sources & evidence

ORD record
ord-d3e2b7cbed234dc7a95e69676da710e3
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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