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Phosphoric Acid → Baricitinib phosphate

HRID 1966177
ノート
印刷プレビュー

反応式

HRID 1966177 の反応式
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[CH:11]=[N:12][N:13]([C:15]3([CH2:24][C:25]#[N:26])[CH2:18][N:17]([S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[CH2:16]3)[CH:14]=2)=[N:3][CH:2]=1.[P:27](=[O:31])([OH:30])([OH:29])[OH:28]>C(#N)C.C(O)C>[P:27](=[O:28])([OH:31])([OH:30])[OH:29].[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[CH:11]=[N:12][N:13]([C:15]3([CH2:24][C:25]#[N:26])[CH2:16][N:17]([S:19]([CH2:22][CH3:23])(=[O:20])=[O:21])[CH2:18]3)[CH:14]=2)=[N:3][CH:2]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 1004Phosphoric AcidHCID 44205240Baricitinib

生成物 1

HCID 44231848Baricitinib phosphate収率 93%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒2 回HCID 6342Acetonitrile溶媒

反応条件

温度
70 °C

実験手順

To a solution of 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile (7, 204 g, 550 mmol) in acetonitrile (5.1 L) and ethanol (1.6 L) was added a solution of phosphoric acid (67.4 g, 688 mmol, 1.25 equiv) in ethanol (800 mL) slowly over 30 min at 70° C. The resulting reaction mixture was stirred at 70° C. for 2 h before being gradually cooled to room temperature with stirring for overnight. The solids were collected by filtration, washed with acetonitrile (160 mL) and dried in vacuum oven at 45° C. for 6 h to afford 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile phosphoric acid salt (240 g, 258.2 g theoretical, 93% yield) as a white solid. For final product: 1H NMR (300 MHz, d6-DMSO) 81.25 (t, 3H), 3.25 (q, 2H), 3.75 (s, 2H), 4.20 (d, 2H), 4.61 (d, 2H), 7.10 (d, 1H), 7.60 (dd, 1H), 8.50 (s, 1H), 8.70 (s, 1H), 8.95 (s, 1H), 12.2 (bs, 1H); MS: m/z calcd. 372.12. found: 372.0.

後処理

  1. customThe resulting reaction mixture
  2. temperaturebefore being gradually cooled to room temperature
  3. stirringwith stirring for overnight
  4. filtrationThe solids were collected by filtration
  5. washwashed with acetonitrile (160 mL)
  6. customdried in vacuum oven at 45° C. for 6 h

出典と根拠

ORDレコード
ord-ee762ebdde3a4533b138032bbbe36a85
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08420629B2

反応ノート

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