Triethylamine → tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

HRID 1623335노트

반응식

HRID 1623335 반응식
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C@@H:27]([CH3:39])[CH2:26]1.[NH2:40][C@@H:41]1[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:43]([CH3:55])[CH2:42]1.C(N(CC)CC)C>CS(C)=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@H:25]2[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[C@@H:27]([CH3:39])[CH2:26]2)=[N:6][CH:7]=1.[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:40][C@@H:41]2[CH2:46][CH2:45][C@@H:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[C@H:43]([CH3:55])[CH2:42]2)=[N:6][CH:7]=1

참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 58127193HCID 58127193, 화합물HCID 86650623tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate

생성물 1

HCID 86650625tert-butyl (1S,2S,4S)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate tert-butyl (1R,2R,4R)-4-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)-2-methylcyclohexylcarbamate

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
100 °C

실험 절차

A mixture of Intermediate B (preparation of intermediate B is described in the intermediate session which is in front of the Examples) (25 mg, 0.075 mmol), tert-butyl (1S,2S,4S)-4-amino-2-methylcyclohexylcarbamate/tert-butyl(1R,2R,4R)-4-amino-2-methylcyclohexylcarbamate (25.8 mg, 0.113 mmol), triethylamine (28 μl, 0.201 mmol) in DMSO (0.25 mL) was heated at 100° C. for 3 days. The mixture was allowed to cool to ambient temperature and diluted with EtOAc (20 mL) and saturated aqueous NaHCO3 solution (10 mL). The separated aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered off and concentrated in vacuo providing crude tert-butyl (1S,2S,4S)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate/tert-butyl (1R,2R,4R)-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)-2-methylcyclohexylcarbamate, which was directly used in the next step without further purification.

후처리

  1. temperatureto cool to ambient temperature
  2. extractionThe separated aqueous layer was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered off
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-1ac8c8ddc6d34bf98e19e0851fe482f1
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778951B2

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