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Diisopropylethylamine → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1011716
ノート
印刷プレビュー

反応式

HRID 1011716 の反応式
CC[N:3]([CH:7]([CH3:9])C)[CH:4](C)C.[F:10][CH2:11][CH:12]([O:15][C:16]1[CH:17]=[C:18]([O:31][C:32]2[N:33]=[CH:34][C:35]([C:38](O)=[O:39])=[N:36][CH:37]=2)[CH:19]=[C:20]([C:22]([NH:24][C:25]2[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=2)=[O:23])[CH:21]=1)[CH2:13][F:14].Cl.N1CCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[N:3]1([C:38]([C:35]2[N:36]=[CH:37][C:32]([O:31][C:18]3[CH:19]=[C:20]([CH:21]=[C:16]([O:15][CH:12]([CH2:13][F:14])[CH2:11][F:10])[CH:17]=3)[C:22]([NH:24][C:25]3[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=3)=[O:23])=[N:33][CH:34]=2)=[O:39])[CH2:4][CH2:9][CH2:7]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 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 12308726Azetidine hydrochlorideHCID 591271395-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid

生成物 1

HCID 16039644
3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide
収率 35.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

DIPEA (0.45 mL, 2.58 mmol) was added to a mixture of 5-[(3-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid (0.28 g, 0.65 mmol), azetidine hydrochloride (121 mg, 1.29 mmol) and HATU (516 mg, 1.36 mmol) in DMF (5 mL) and stirred at RT for 72 hours. Ethyl acetate (40 mL) was added and the organics washed with water (2×30 mL), brine (30 mL), dried (MgSO4), filtered and reduced in vacuo to give a yellow oil which was chromatographed on silica, eluting with 0-100% ethyl acetate in isohexane, to give the desired compound (109 mg). 1H NMR δ (CDCl3): 2.32 (quin, 2H), 3.70 (s, 3H), 4.19 (t, 2H), 4.54-4.72 (m, 7H), 6.73 (s, 1H), 6.93 (t, 1H), 7.22 (d, 1H), 7.25 (s, 1H), 7.34 (s, 1H), 8.28 (d, 1H), 8.78 (d, 1H), 8.80 (s, 1H); m/z 473 (M+H)+

後処理

  1. washthe organics washed with water (2×30 mL), brine (30 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customto give a yellow oil which
  5. customwas chromatographed on silica
  6. washeluting with 0-100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-2ba7135eddb14b6586c41ab2a92a7bd4
出典データセット
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07977328B2

反応ノート

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