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

HRID 879167Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 879167
[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]

Komponenten

4

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-715571212a0049bb84a335a62768e360
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987457B2

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