1,2-Dichloroethane → (R)-(4'-chlorobiphenyl-2-yl)(1-(4-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonylcarbamoyl)phenyl)piperidin-4-yl)methyl diethyl phosphate, hydrochloride salt

HRID 1476356Notes

Reaction equation

HRID 1476356 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([O:30][P:31]([O:36][CH2:37][CH3:38])([O:33][CH2:34][CH3:35])=[O:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.[O:39]1[CH2:44][CH2:43][N:42]([CH2:45][CH2:46][C@@H:47]([NH:56][C:57]2[CH:62]=[CH:61][C:60]([S:63]([NH2:66])(=[O:65])=[O:64])=[CH:59][C:58]=2[S:67]([C:70]([F:73])([F:72])[F:71])(=[O:69])=[O:68])[CH2:48][S:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH2:41][CH2:40]1.C(Cl)CCl>C(Cl)Cl>[ClH:1].[P:31]([O:36][CH2:37][CH3:38])([O:33][CH2:34][CH3:35])([O:30][C@@H:14]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:29]=[CH:28][C:24]([C:25](=[O:26])[NH:66][S:63]([C:60]3[CH:61]=[CH:62][C:57]([NH:56][C@H:47]([CH2:46][CH2:45][N:42]4[CH2:43][CH2:44][O:39][CH2:40][CH2:41]4)[CH2:48][S:49][C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)=[C:58]([S:67]([C:70]([F:72])([F:73])[F:71])(=[O:69])=[O:68])[CH:59]=3)(=[O:64])=[O:65])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1)=[O:32]

Participants

5

Reactant 3

HCID 111,2-Dichloroethane2×HCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamide2×HCID 58080188(R)-4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acid2×

Product 1

HCID 131732790(R)-(4'-chlorobiphenyl-2-yl)(1-(4-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonylcarbamoyl)phenyl)piperidin-4-yl)methyl diethyl phosphate, hydrochloride salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-4-(4-((4′-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 120, 371 mg, 0.66 mmol), (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 368 mg, 0.66 mmol), EDC (255 mg, 1.33 mmol), TEA (0.185 ml, 1.33 mmol), and DCE (5 ml) were stirred at r.t. for 2 hours. The mixture was diluted with DCM (15 ml) and adsorbed onto silica gel. Purification by column chromatography (ISCO, eluting with 0→10% MeOH/DCM over 19 minutes followed by elution with 0→10% 2M NH3/MeOH/DCM over 24 minutes) gave a residue which was further purified by reverse phase HPLC, according to the conditions:

Workup

  1. customPurification
  2. washby column chromatography (ISCO, eluting with 0→10% MeOH/DCM over 19 minutes followed by elution with 0→10% 2M NH3/MeOH/DCM over 24 minutes)
  3. customgave a residue which
  4. customwas further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-4b8f52d6c7a648ac9f0b311b39df44ce
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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