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Phosphoric Acid → Baricitinib phosphate

HRID 1966177
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HRID 1966177 반응식
[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
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참가 물질

5

반응물 2

HCID 1004Phosphoric AcidHCID 44205240Baricitinib

생성물 1

HCID 44231848Baricitinib phosphate수율 93%

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 6342Acetonitrile용매

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온도
70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ee762ebdde3a4533b138032bbbe36a85
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08420629B2

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