N,N-Dimethylethylenediamine → (1R,2R)-2-((6-((6-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

HRID 1848054노트

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HRID 1848054 반응식
Br[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[CH3:29][S:30]([O-:32])=[O:31].[Na+].CN(C)CCN>CS(C)=O>[CH3:29][S:30]([C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1)(=[O:32])=[O:31]

참가 물질

5

반응물 3

HCID 66053N,N-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 86681028(1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

생성물 1

HCID 71550700(1R,2R)-2-((6-((6-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol수율 12%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
125 °C

실험 절차

A stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (100 mg, 0.218 mmol) from Example 29, sodium methanesulfinate (90 mg, 0.436 mmol) and unsymmetrical N,N-dimethylethylene diamine (6 mg, 0.066 mmol) in anhydrous DMSO (1 mL) at rt was flushed with a stream of argon for 15 min. To the resulting mixture was added copper (I) trifluoromethane-sulfonate benzene complex (20 mg, 0.0328 mmol). The reaction vessel was sealed and the mixture was heated with stirring at 125° C. for 5 h. After cooling to rt, the reaction mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(methylsulfonyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (12 mg, 12%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.85-8.95 (br m, 2H), 8.61 (s, 1H), 8.02 (d, J=7.3 Hz, 1H), 7.69 (s, 1H), 7.18-7.35 (m, 2H), 5.56 (s, 2H), 4.79 (br s, 1H), 3.25-3.60 (m, 5H), 2.03 (m, 1H), 1.87 (m, 1H), 1.55-1.70 (m, 2H), 1.08-1.36 (m, 4H). LCMS (ESI) m/z 458 (M+H)+.

후처리

  1. customwas flushed with a stream of argon for 15 min
  2. additionTo the resulting mixture was added copper (I) trifluoromethane-sulfonate benzene complex (20 mg, 0.0328 mmol)
  3. customThe reaction vessel was sealed
  4. temperaturethe mixture was heated
  5. temperatureAfter cooling to rt
  6. customthe reaction mixture was purified directly by reverse-phase
  7. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

출처 및 근거

ORD 기록
ord-74ea73a9c0734b05bad0216f560eb836
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952058B2

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