5-Amino-2,3-dihydro-isoindol-1-one → 5-[(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]isoindolin-1-one

HRID 1039088

반응식

HRID 1039088 반응식
CC1C=CC(S(O[CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)[CH2:19][CH2:18]2)(=O)=O)=CC=1.[NH2:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[C:36](=[O:40])[NH:35][CH2:34]2>S1(CCCC1)(=O)=O.O>[Cl:29][C:26]1[CH:27]=[N:28][C:23]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][NH:30][C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[C:36](=[O:40])[NH:35][CH2:34]4)[CH2:22][CH2:21]2)=[N:24][CH:25]=1

참가 물질

5

반응물 2

HCID 219562395-Amino-2,3-dihydro-isoindol-1-oneHCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

생성물 1

HCID 509387625-[(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]isoindolin-1-one

시약·촉매·용매 2

HCID 962Water용매HCID 31347Sulfolane용매

반응 조건

온도
120 °C

실험 절차

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate from step 1 of Example 5 (100 mg, 0.23 mmol) was dissolved in sulfolane and 5-aminoisoindolin-1-one (68 mg, 0.46 mmol) from step 3 of this example added. The mixture was at stirred 110° C. for 3 and at 120° C. for 2 hours. The mixture was cooled to RT, diluted with 4:1 water:saturated sodium bicarbonate (40 ml), extracted with EtOAc (3×30 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered, the volatiles removed in vacuum. The product was purified by chromatography on SiO2 eluting with 80% acetone:hexanes to give the titled compound. LRMS calc: 411.18; obs: 412.08 (M+1). Compounds reported in Table 7 are prepared by a general procedure analogous to that described in Example 44 above.

후처리

  1. temperatureThe mixture was cooled to RT
  2. extractionsaturated sodium bicarbonate (40 ml), extracted with EtOAc (3×30 ml)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe volatiles removed in vacuum
  7. customThe product was purified by chromatography on SiO2 eluting with 80% acetone

출처 및 근거

ORD 기록
ord-c1fc6020b01d4eca9cc9dfde269c8792
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08552022B2

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