Dichloromethane → HCID 86621216, 화합물

HRID 1855242노트

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HRID 1855242 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

HCID 86621216HCID 86621216, 화합물

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 962Water용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-73bcde69b8d348bfb30294b1bf2f6a2a
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962856B2

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