1,2-Dichloroethane → 3-(1-(2-((5S)-2-(2-(2-(piperidin-1-yl)ethylamino)-3-fluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetyl)piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one

HRID 1695932Notes

Reaction equation

HRID 1695932 reaction equation
[N:1]1([CH2:7][CH2:8][NH:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[CH:17]2[N:21]([CH2:22][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:20](=[O:28])[C@H:19]([CH2:29][C:30]([OH:32])=O)[S:18]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH2:45][CH2:44][C:43]3[CH:46]=[CH:47][CH:48]=[CH:49][C:42]=3[NH:41][C:40]2=[O:50])[CH2:35][CH2:34]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O.CCOC(C)=O>[N:1]1([CH2:7][CH2:8][NH:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[CH:17]2[N:21]([CH2:22][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:20](=[O:28])[C@H:19]([CH2:29][C:30]([N:33]3[CH2:34][CH2:35][CH:36]([N:39]4[CH2:45][CH2:44][C:43]5[CH:46]=[CH:47][CH:48]=[CH:49][C:42]=5[NH:41][C:40]4=[O:50])[CH2:37][CH2:38]3)=[O:32])[S:18]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 577743712-((5S)-2-(2-(2-(piperidin-1-yl)ethylamino)-3-fluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid

Product 1

HCID 252056893-(1-(2-((5S)-2-(2-(2-(piperidin-1-yl)ethylamino)-3-fluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetyl)piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((5S)-2-(2-(2-(piperidin-1-yl)ethylamino)-3-fluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid (319.0 mg, 0.685 mmol), 4,5-dihydro-3-(piperidin-4-yl)-1H-benzo[d][1,3]diazepin-2(3H)-one (336.1 mg, 1.370 mmol), EDC (262.6 mg, 1.370 mmol) and HOBT (209.8 mg, 1.370 mmol) were stirred at RT in DMF (4 mL) overnight. Transferred mixture to a separatory funnel with EtOAc and water. The aqueous layer was extracted with EtOAc (3×), the organic layers were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude was dissolved in DMSO and purified by reverse phase semi-prep chromatography (CH3CN/water mobile phase) to give 3-(1-(2-((5S)-2-(2-(2-(piperidin-1-yl)ethylamino)-3-fluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetyl)piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one. LC/MS: 692.34 (M+1) Rt=2.24 min (10-90% 3/5 min (gradient/run) w/formic acid).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×)
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude was dissolved in DMSO
  6. custompurified by reverse phase semi-prep chromatography (CH3CN/water mobile phase)

Sources & evidence

ORD record
ord-f1d371b67f1041bca822aa927c446263
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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