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Diisopropylethylamine → 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide

HRID 1050130
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HRID 1050130 반응식
[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=O)=[C:22]([F:30])[CH:21]=1)[CH3:2].[NH2:31][C:32]1[CH:33]=[C:34]([C:43]([F:46])([F:45])[F:44])[C:35]([C:38]([CH3:42])([CH3:41])[CH2:39][OH:40])=[N:36][CH:37]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:31][C:32]2[CH:37]=[N:36][C:35]([C:38]([CH3:42])([CH3:41])[CH2:39][OH:40])=[C:34]([C:43]([F:46])([F:44])[F:45])[CH:33]=2)=[O:29])=[C:22]([F:30])[CH:21]=1)[CH3:2]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 904227052-(4-(4-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acidHCID 904232762-(5-Amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropan-1-ol

생성물 1

HCID 90422974
2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide
수율 26.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (50 mg, 0.122 mmol), 2-(5-amino-3-(trifluoromethyl)pyridin-2-yl)-2-methylpropan-1-ol (28.5 mg, 0.122 mmol), HATU (92 mg, 0.243 mmol) and DIEA (0.064 mL, 0.365 mmol) in DCM (10 mL) was stirred at 25° C. After LCMS analysis showed the starting material was consumed, the mixture was washed with H2O. The organic layer was washed with brine and dried over Na2SO4 and filtered. The filtrate was concentrated to give the crude product, which was purified by preparative TLC (DCM/MeOH=20/1) to yield 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide (20 mg, 0.032 mmol, 26% yield): 1H NMR (400 MHz, CD3OD) δ 8.95 (br. s., 1H), 8.50 (s, 1H), 7.99 (s, 1H), 7.43-7.39 (m, 3H), 7.30-7.24 (m, 2H), 6.95-6.91 (m, 2H), 6.48 (s, 1H), 5.30 (s, 2H), 4.16-4.11 (m, 2H), 3.87-3.79 (m, 6H), 1.40-1.38 (m, 9H); ES-LCMS m/z: 628.3 (M+H).

후처리

  1. customwas consumed
  2. washthe mixture was washed with H2O
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customto give the crude product, which
  8. customwas purified by preparative TLC (DCM/MeOH=20/1)

출처 및 근거

ORD 기록
ord-f9441274bb344a5184604d79dcc06230
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09382238B2

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