Dichloromethane → HCID 86621216, Verbindung

HRID 1673140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1673140
[NH2:1][CH:2]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])[C:3]1[S:7][C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:22]=[CH:21][C:17]4[O:18][CH2:19][O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])=[N:5][C:4]=1[CH3:23].[Si:31]([O:38][C@H:39]([CH2:43]Cl)[CH2:40][CH:41]=O)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].[BH4-].[Na+].C(Cl)Cl>CO.O>[O:18]1[C:17]2[CH:21]=[CH:22][C:14]([C:11]3([C:9]([NH:8][C:6]4[S:7][C:3]([CH:2]([N:1]5[CH2:41][CH2:40][C@H:39]([O:38][Si:31]([C:34]([CH3:36])([CH3:35])[CH3:37])([CH3:32])[CH3:33])[CH2:43]5)[C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[Cl:30])=[C:4]([CH3:23])[N:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20][CH2:19]1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 13963152HCID 13963152, VerbindungHCID 76672719N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Produkt 1

HCID 86621216HCID 86621216, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittel2×HCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution of N-(5-(amino(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (Isomer A) (450 mg, 1.02 mmol) in MeOH (5 mL) was added (S)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanal (289 mg, 1.22 mmol). The reaction mixture was stirred at room temperature for 20 min before NaBH4 (58 mg, 1.53 mmol) was added. Stirring was continued at room temperature for 3 h. After approximately 1 h some precipitate/gum started to form in the reaction solution so MeOH (5 mL) and CH2Cl2 (2 mL) were added to keep everything in solution. The reaction was diluted with H2O and extracted with EtOAc. The combined organic layers was washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (0-25% EtOAc/hexanes) to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(((S)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) as a pale yellow solid (470 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.83 (dd, J=8.1, 1.6 Hz, 1H), 7.28-7.25 (m, 2H), 7.13 (m, 1H), 6.88-6.83 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 6.00 (s, 2H), 5.08 (s, 1H), 4.33 (m, 1H), 2.94 (dd, J=9.9, 6.3 Hz, 1H), 2.67 (td, J=8.3, 3.4 Hz, 1H), 2.53 (q, J=8.4 Hz, 1H), 2.37 (s, 3H), 2.17 (dd, J=9.9, 4.7 Hz, 1H), 2.00 (m, 1H), 1.74-1.61 (m, 3H), 1.17 (m, 2H), 0.86 (m, 9H), 0.01 (s, 3H), −0.01 (s, 3H); HPLC ret. time 3.45 min, 10-99% CH3CN, 5 min run; ESI-MS 626.5 m/z (MH+).

Aufarbeitung

  1. additionwas added
  2. waitAfter approximately 1 h some precipitate/gum started
  3. additionwere added
  4. extractionextracted with EtOAc
  5. washThe combined organic layers was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. custompurified by column chromatography (0-25% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-778652db69bb4ec49b4f9f584b3b599c
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07999113B2

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