4-Hydroxypyrimidine → 3-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-pyrimidin-4-one

HRID 1692024노트

반응식

HRID 1692024 반응식
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[N:22]1[CH:27]=[CH:26][C:25](=[O:28])[NH:24][CH:23]=1.CN[C@@H]1CCCC[C@H]1NC>N1C=CC=CC=1.CCOCC.[Cu].[Cu]I>[N:14]1([C@@H:11]2[CH2:12][CH2:13][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([N:24]5[C:25](=[O:28])[CH:26]=[CH:27][N:22]=[CH:23]5)[CH:21]=[CH:20][C:5]=4[N:6]=3)[CH2:10]2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

참가 물질

8

반응물 3

HCID 206954-HydroxypyrimidineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 44124247(R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

생성물 1

HCID 441253323-[2-((R)-3-piperidin-1-yl-pyrrolidin-1-yl)-benzothiazol-6-yl]-3H-pyrimidin-4-one

시약·촉매·용매 4

HCID 23978Copper촉매HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 1049Pyridine용매HCID 3283Diethyl Ether용매

실험 절차

A solution of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 80 mg, 0.218 mmol), pyrimidin-4(3H)-one (31.5 mg, 0.328 mmol), (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (31.1 mg, 0.218 mmol), copper (27.8 mg, 0.437 mmol) and copper(I) iodide (8.32 mg, 0.044 mmol) in pyridine (3 ml) was heated in a microwave reactor to 200° C. for 30 minutes. The mixture was diluted with ether (20 mL) and washed with water, a small amount of aqueous NH4OH and brine. The organic layer was separated and dried with MgSO4 and concentrated under reduced pressure. The residue obtained was chromatographed on silica gel column eluting with 3% (9:1 methanol:concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.43-1.52 (m, 2H), 1.58-1.69 (m, 4H), 1.94-2.11 (m, 1H), 2.25-2.37 (m, 1H), 2.39-2.58 (m, 4H), 2.96-3.09 (m, 1H), 3.40-3.63 (m, 2H), 3.72-3.92 (m, 2H), 6.56 (d, J=6.74 Hz, 1H), 7.22 (dd, J=8.72, 2.38 Hz, 1H), 7.62 (d, J=2.38 Hz, 1H), 7.65 (d, J=8.33 Hz, 1H), 7.94 (d, J=6.74 Hz, 1H), 8.20 (s, 1H); MS (DCI/NH3) m/z 382 (M+H)+.

후처리

  1. washwashed with water
  2. customThe organic layer was separated
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customwas chromatographed on silica gel column
  7. washeluting with 3% (9:1 methanol:concentrated NH4OH) in dichloromethane

출처 및 근거

ORD 기록
ord-e6d0e5fe977240498d4f7932032c907f
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08153813B2

반응 노트

불러오는 중…