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Methanol → 3-(5-Ethynylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile trifluoroacetate

HRID 1962754
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HRID 1962754 반응식
C[Si](C)(C)CCOC[N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([C:25]4[CH:26]=[N:27][CH:28]=[C:29]([C:31]#[C:32][Si](C)(C)C)[CH:30]=4)[CH2:22][C:23]#[N:24])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.C(Cl)Cl.[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43].[OH-].[K+].CO>>[C:42]([OH:48])([C:44]([F:47])([F:46])[F:45])=[O:43].[F:45][C:44]([F:47])([F:46])[C:42]([OH:48])=[O:43].[C:31]([C:29]1[CH:30]=[C:25]([CH:21]([N:19]2[CH:20]=[C:16]([C:15]3[C:10]4[CH:9]=[CH:8][NH:7][C:11]=4[N:12]=[CH:13][N:14]=3)[CH:17]=[N:18]2)[CH2:22][C:23]#[N:24])[CH:26]=[N:27][CH:28]=1)#[CH:32]
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참가 물질

7

반응물 5

HCID 887MethanolHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 57477894HCID 57477894, 화합물

생성물 2

HCID 6422Trifluoroacetic acid수율 0.2%
HCID 86632619
3-(5-Ethynylpyridin-3-yl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile trifluoroacetate
수율 36%

실험 절차

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-{5-[(trimethylsilyl)ethynyl]pyridin-3-yl}propanenitrile (0.050 g, 0.000092 mol) was dissolved in DCM (5.0 mL, 0.078 mol) and TFA (2.0 mL, 0.026 mol). The reaction mixture was stirred at room temperature, for 90 minutes and was concentrated in vacuo. The dry residue dissolved in methanol cooled in an ice bath and a solution of potassium hydroxide (0.482 g, 0.00859 mol) in methanol (10 mL, 0.2 mol) was added. The reaction solution was stirred for 30 min was concentrated and the crude product was purified by preparative HPLC eluting with a water:ACN gradient with 0.2% TFA, to give the title compound as a white amorphous solid (15 mg, 35.85%). LCMS (M+1)+: 340, 1H NMR (400 MHz, DMSO-d6): δ 12.1 (bs, 1H), 9.02 (s, 1H), 8.80 (s, 1H), 8.70 (m, 2H), 8.48 (s, 1H), 8.00 (s, 1H), 7.80 (d, 1H), 7.15 (d, 1H), 6.20 (m, 1H), 4.82 (s, 1H), 3.90 (m, 1H), 3.70 (m, 1H).

후처리

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe dry residue dissolved in methanol
  3. temperaturecooled in an ice bath
  4. stirringThe reaction solution was stirred for 30 min
  5. concentrationwas concentrated
  6. customthe crude product was purified by preparative HPLC
  7. washeluting with a water

출처 및 근거

ORD 기록
ord-7950ccbf0d3f4f33becfe1cf6c04743d
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08415362B2

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