Methanesulfonyl chloride → (1R,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate

HRID 879167노트

반응식

HRID 879167 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]([C:15]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][C:23]=2[C@H:24]2[CH2:29][C@@H:28]([NH:30]C(=O)OC(C)(C)C)[C@H:27]([OH:38])[C@@H:26]([CH3:39])[CH2:25]2)=[O:16])[CH:12]=[CH:11][C:10]=1[F:40].[CH3:41][S:42](Cl)(=[O:44])=[O:43]>C(Cl)Cl>[CH3:41][S:42]([O:38][C@@H:27]1[C@@H:26]([CH3:39])[CH2:25][C@@H:24]([C:23]2[CH:22]=[CH:21][N:20]=[CH:19][C:18]=2[NH:17][C:15](=[O:16])[C:13]2[CH:12]=[CH:11][C:10]([F:40])=[C:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[N:14]=2)[CH2:29][C@H:28]1[NH2:30])(=[O:44])=[O:43]

참가 물질

4

반응물 2

HCID 31297Methanesulfonyl chlorideHCID 86639738tert-butyl (1R,2R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate

생성물 1

HCID 72551165(1R,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate수율 31%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl (1R,2R,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate (1.0 equiv.) in CH2Cl2 was added TEA (4.0 equiv.) and MsCl (2.0 equiv.). The capped solution was stirred for 5 minutes and then the homogeneous solution was left standing at rt for 16 hrs. The volatiles were removed in vacuo, the residue was dissolved in DMSO, purified by RP HPLC and the product fractions were lyophilized directly. The Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles were removed in vacuo and the residue was dissolved in DMSO and purified by RP-HPLC. The product fractions were lyophilized directly to yield (1R,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate in 31% yield. LC/MS (m/z)=535.2 (MH+), Rt=0.61 min.

후처리

  1. waitthe homogeneous solution was left
  2. waitstanding at rt for 16 hrs
  3. customThe volatiles were removed in vacuo
  4. dissolutionthe residue was dissolved in DMSO
  5. custompurified by RP HPLC
  6. additionThe Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles
  7. customwere removed in vacuo
  8. dissolutionthe residue was dissolved in DMSO
  9. custompurified by RP-HPLC

출처 및 근거

ORD 기록
ord-715571212a0049bb84a335a62768e360
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987457B2

반응 노트

불러오는 중…