Acetic Acid → 1-[1-[(3S)-3-(3,4-Dichlorophenyl)-4-(5-phenyltetrazol-1-yl)butyl]-piperidin-4-yl]tetrahydropyrimidin-2-one dihydrochloride

HRID 277313Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 277313
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]2[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:17][N:16]=[N:15]2)[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH:25]1[CH2:30][CH2:29][CH:28]([N:31]2[CH2:36][CH2:35][CH2:34][NH:33][C:32]2=[O:37])[CH2:27][CH2:26]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.ClCCl.C(=O)(O)[O-].[Na+]>[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]([CH2:13][N:14]2[C:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[N:17][N:16]=[N:15]2)[CH2:10][CH2:11][N:25]2[CH2:30][CH2:29][CH:28]([N:31]3[CH2:36][CH2:35][CH2:34][NH:33][C:32]3=[O:37])[CH2:27][CH2:26]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 155726661-(Piperidin-4-yl)-1,3-diazinan-2-oneHCID 57095043(3S)-3-(3,4-dichlorophenyl)-4-(5-phenyltetrazol-1-yl)-butyraldehyde

Produkt 1

HCID 213086331-[1-[(3S)-3-(3,4-Dichlorophenyl)-4-(5-phenyltetrazol-1-yl)butyl]-piperidin-4-yl]tetrahydropyrimidin-2-one dihydrochlorideAusbeute 185,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittel3×HCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

(3S)-3-(3,4-dichlorophenyl)-4-(5-phenyltetrazol-1-yl)-butyraldehyde (0.90 g) in methanol (6 mL) and dichloromethane (2 mL) was added to a solution of 1-(piperidin-4-yl)tetrahydropyrimidin-2-one (0.458 g) and acetic acid (0.14 mL) in methanol (5 mL). After 40 minutes, sodium cyanoborohydride (0.157 g) in methanol (5 mL) was added in a single portion. After being stirred for 2 hours, the reaction mixture was diluted with aqueous sodium bicarbonate, stirred for 30 minutes, and extracted with dichloromethane. The organic extracts were dried, evaporated, and chromatographed, with dichloromethane:methanol (gradient 98:2, 70:30) as eluent. The purified material was dissolved in dichloromethane, precipitated out as the hydrochloride salt with ethereal hydrogen chloride, evaporated, and placed under high vacuum overnight to give the title compound as a white solid (0.928 g); NMR (CD3OD): 7.61-7.47 (m,3), 7.30 (m,2), 7.21 (d,1, J=8.2), 7.03 (d,1, J=2.1), 6.75 (dd,1, J=2.1, 8.3), 4.94 (dd,1, J=4.8, 14.2), 4.74 (dd,1, J=9.4, 14.2), 4.34 (m,1), 3.58 (m,2), 3.25 (m,5), 3.15-2.98 (m,3), 2.76 (m,1), 2.33-2.11 (m,4), 1.90 (m,4); MS: m/z=528(M+1). Analysis for C26H31Cl2N7O.0.15 Et2O.2.50 HCl: Calculated: C, 50.65; H, 5.59; N, 15.54; Found: C, 50.58; H, 5.61; N, 15.27.

Aufarbeitung

  1. stirringstirred for 30 minutes
  2. extractionextracted with dichloromethane
  3. customThe organic extracts were dried
  4. customevaporated
  5. customchromatographed, with dichloromethane
  6. dissolutionThe purified material was dissolved in dichloromethane
  7. customprecipitated out as the hydrochloride salt with ethereal hydrogen chloride
  8. customevaporated
  9. customplaced under high vacuum overnight

Quellen und Nachweise

ORD-Eintrag
ord-62ec95730b3141f48b9e73cf28bd7c3d
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06355695B1

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