Hydrochloric Acid → N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(oxan-3-yloxy)phenyl]-5-fluoropyridine-2-carboxamide

HRID 1499618ノート

反応式

HRID 1499618 の反応式
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][O:11][CH2:10]2)[CH:5]=[C:4]([F:15])[C:3]=1[C:16]1[N:21]=[C:20]([C:22]([NH:24][C:25]2[C:26]([N:35]3[CH2:40][C@H:39]([CH3:41])[CH2:38][C@H:37]([NH:42]C(=O)OC(C)(C)C)[CH2:36]3)=[C:27]3[CH2:33][CH2:32][CH:31]([OH:34])[C:28]3=[N:29][CH:30]=2)=[O:23])[CH:19]=[CH:18][C:17]=1[F:50].Cl.O1CCOCC1>>[NH2:42][C@H:37]1[CH2:38][C@@H:39]([CH3:41])[CH2:40][N:35]([C:26]2[C:25]([NH:24][C:22]([C:20]3[CH:19]=[CH:18][C:17]([F:50])=[C:16]([C:3]4[C:2]([F:1])=[CH:7][C:6]([O:8][CH:9]5[CH2:14][CH2:13][CH2:12][O:11][CH2:10]5)=[CH:5][C:4]=4[F:15])[N:21]=3)=[O:23])=[CH:30][N:29]=[C:28]3[CH:31]([OH:34])[CH2:32][CH2:33][C:27]=23)[CH2:36]1

参加物

4

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86726835tert-butyl ((3S,5R)-1-{3-[({6-[2,6-difluoro-4-(tetrahydro-2H-pyran-3-yloxy)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

生成物 1

HCID 86726836N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl]-6-[2,6-difluoro-4-(oxan-3-yloxy)phenyl]-5-fluoropyridine-2-carboxamide

実験手順

The alcohol intermediate made above was treated with 4.0 M HCl in dioxane (1 mL, 5 mmol) at room temperature overnight. The solution was concentrated under reduced pressure and the resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to give two separated diastereoisomers of the title compound as white powders.

後処理

  1. concentrationThe solution was concentrated under reduced pressure
  2. customthe resulting residue was purified by preparative LCMS (Waters SunFire™ C18 column, 19 mm×100 mm, 5 μm particle size
  3. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

出典と根拠

ORDレコード
ord-ff5feaa540ba402b96d56f400f66a9b6
出典データセット
uspto-grants-2015_12
特許番号
US09200004B2

反応ノート

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