Water → (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

HRID 1691992노트

반응식

HRID 1691992 반응식
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([Br:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl.Cl.[NH:14]1[CH2:18][CH2:17][C@@H:16]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:15]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Br:11][C:9]1[CH:8]=[CH:7][C:5]2[N:6]=[C:2]([N:14]3[CH2:18][CH2:17][C@@H:16]([N:19]4[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]4)[CH2:15]3)[S:3][C:4]=2[CH:10]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 20498716-Bromo-2-chlorobenzothiazoleHCID 669057171-[(3R)-pyrrolidin-3-yl]piperidine dihydrochloride

생성물 1

HCID 44124247(R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

A stirred mixture of 2-chloro-6-bromobenzothiazole (2.48 g, 10.0 mmol), (R)-1-(pyrrolidin-3-yl)piperidine dihydrochloride (Reference Example 5c, 2.73 g, 0.0120 mole), and potassium carbonate (6.00 g, 0.04438 mole) in N,N-dimethylformamide (15 mL) was heated to 100° C. with an oil bath for 15 hours. The reaction mixture was cooled to room temperature then poured into water (300 mL). The resulting precipitate was collected by filtration and the filter cake was rinsed with water (600 mL). The solid was dissolved in dichloromethane and the solution was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give a solid that was crystallized from hot ethyl acetate to give (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD3OD) δ ppm 1.46-1.55 (m, 2H), 1.65 (pentet, J=5 Hz, 4H), 1.92-2.07 (m, 1H), 2.29-2.39 (m, 1H), 2.43-2.64 (m, 4H), 3.00-3.12 (m, 1H), 3.33-3.41 (m, 1H), 3.46-3.57 (m, 1H), 3.66-3.75 (m, 1H), 3.77-3.86 (m, 1H), 4.07-4.35 (m, 4H), 7.35 (d, J=9 Hz, 1H), 7.40 (dd, J=2, 9 Hz, 1H), 7.81 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 366 (M+H)+.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe resulting precipitate was collected by filtration
  3. washthe filter cake was rinsed with water (600 mL)
  4. dissolutionThe solid was dissolved in dichloromethane
  5. dry with materialthe solution was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto give a solid
  9. customthat was crystallized from hot ethyl acetate

출처 및 근거

ORD 기록
ord-1604f0389a064f248884f659d109f0e5
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08153813B2

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