Hydrochloric Acid → (3R)-3-[(1S)-1-(3,4-Dichlorophenyl)-3-(4-(2-methylsulfinylphenyl)-piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one hydrochloride

HRID 1082197노트

반응식

HRID 1082197 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([C@@H:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]2[CH3:23])[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:24][S:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)=[O:26].C([BH3-])#N.[Na+].Cl>CO.C(=O)(O)[O-].[Na+].C(N(CC)CC)C.C(O)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([C@@H:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]2[CH3:23])[CH2:10][CH2:11][N:36]2[CH2:37][CH2:38][CH:33]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[S:25]([CH3:24])=[O:26])[CH2:34][CH2:35]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 187003874-(2-(Methylsulfinyl)phenyl)piperidineHCID 57040947(3S)-3-(3,4-Dichlorophenyl)-3-((1R)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propionaldehyde

생성물 1

HCID 70111254(3R)-3-[(1S)-1-(3,4-Dichlorophenyl)-3-(4-(2-methylsulfinylphenyl)-piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one hydrochloride수율 90.2%

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 887Methanol용매HCID 8471Triethylamine용매HCID 516892Sodium Bicarbonate용매

실험 절차

A solution of (3S)-3-(3,4-dichlorophenyl)-3-[(1R)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl]propionaldehyde (0.54 g) in methanol (10 mL) was treated with 4-(2-methylsulfinylphenyl)piperidine (0.61 g) and the pH was adjusted to 3 with acetic acid and triethylamine. After treating with sodium cyanoborohydride (189 g) the reaction mixture was stirred at ambient temperature for 16 hours, acidified with 10% hydrochloric acid, stirred for 15 minutes and then diluted with a saturated solution of sodium bicarbonate. Upon extraction with dichloromethane, the organic layer was dried and evaporated to obtain the crude product. This material was purified by chromatography, with 20:1 dichloromethane:methanol as the eluent to give the desired 3-[1-(3,4-dichlorophenyl)-3-(4-(2-methylsulfinylphenyl)piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one (0.414 g). This material was transformed into the hydrochloride salt as follows. The material was dissolved in dichloromethane (2 mL) and treated with hydrochloric acid in ether (2 mL). The resulting solution was diluted with anhydrous ether (80 mL), stirred for 4 hours, and the resulting precipitate was collected to afford the title compound (0.35 g); mp 180°-188° C.; MS: m/z=555<M+1); NMR(CD3SOCD3): 2.0 (broad,2), 2.3 (broad,2), 2.7 (s,3), 3.1 (s,3), 3.6 (t,2, J=15), 3.76 (m,1), 4.9 (d,1, J=2.4), 6.8 (d,1, J=7.8), 7.0 (s,1), 7.3-7.98 (m,9). Analysis for C30H32C.HCl.H2O: Calculated: C, 59.07; H, 5.78; N, 4.59; Found: C, 59.06; H, 5.72; N, 4.45.

후처리

  1. stirringstirred for 15 minutes
  2. extractionUpon extraction with dichloromethane
  3. customthe organic layer was dried
  4. customevaporated
  5. customto obtain the crude product
  6. customThis material was purified by chromatography, with 20:1 dichloromethane

출처 및 근거

ORD 기록
ord-30a1f7bc4ef94cb080de5700acc98388
출처 데이터셋
uspto-grants-1996_12
특허 번호
US05589489

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