HCID 86703399、化合物 → Saxagliptin

HRID 1184044

反応式

HRID 1184044 の反応式
[C:1]([C@@H:3]1[CH2:8][C@H:7]2[C@H:5]([CH2:6]2)[N:4]1[C:9](=[O:33])[C@@H:10]([NH:22]C(=O)OCC1C=CC=CC=1)[C:11]12[CH2:20][CH:15]3[CH2:16][CH:17]([CH2:19][C:13]([OH:21])([CH2:14]3)[CH2:12]1)[CH2:18]2)#[N:2]>C(#N)C.[Pd]>[CH2:8]1[C@@H:3]([C:1]#[N:2])[N:4]([C:9]([C@@H:10]([NH2:22])[C:11]23[CH2:12][C:13]4([OH:21])[CH2:19][CH:17]([CH2:16][CH:15]([CH2:14]4)[CH2:20]2)[CH2:18]3)=[O:33])[C@@H:5]2[C@H:7]1[CH2:6]2

参加物

4

反応物 1

HCID 86703399HCID 86703399、化合物

生成物 1

HCID 11243969Saxagliptin

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 6342Acetonitrile溶媒

実験手順

To a solution of benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo-ethyl]carbamate (10 gm) (formula-IX) in acetonitrile, 5% Pd/C (50% wet, 1 gm) was added. Hydrogen gas was bubbled through the reaction mass for 4 hrs at 20-25° C. After complete conversion of starting material, the reaction mass was filtered, the filtrate was evaporated to yield SAXAGLIPTIN free base of formula-I as a foamy solid. The solid was dissolved in ethyl acetate (50 ml) and concentrated hydrochloric acid (2.4 ml) was added at 5-10° C. The white solid formed was filtered to yield 7.8 gm (99%) of SAXAGLIPTIN dihydrate mono-hydrochloride M.P: 228-230° C., HPLC: 99.7% (A) and the content of the impurity cyclic amidine: 0.05% (A), H1NMR (300 MHz, Methanol-d4): 0.87-1.13 (m, 2H), 1.48-1.7 (m, 12H), 1.89-1.96 (ddd, 1H), 2.19 (s, 1H), 2.22-2.28 (dd, 1H), 2.49 (ddd, 1H), 3.83-3.88 (ddd, 1H), 4.19 (s, 1H), 5.08-5.12 (dd, 1H).

後処理

  1. customHydrogen gas was bubbled through the reaction mass for 4 hrs at 20-25° C
  2. filtrationAfter complete conversion of starting material, the reaction mass was filtered
  3. customthe filtrate was evaporated

出典と根拠

ORDレコード
ord-63382f4c0052437d8270fe1c28fe898d
出典データセット
uspto-grants-2014_03
特許番号
US08664443B2

関連ノート

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