Ammonia → 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanamide

HRID 710668ノート

反応式

HRID 710668 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:33])[CH:18]([N:23]4[C:27]([CH3:28])=[CH:26][C:25]([C:29]([F:32])([F:31])[F:30])=[N:24]4)[CH2:19][C:20](O)=[O:21])[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.N.C[N:36](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:33])[CH:18]([N:23]4[C:27]([CH3:28])=[CH:26][C:25]([C:29]([F:32])([F:30])[F:31])=[N:24]4)[CH2:19][C:20]([NH2:36])=[O:21])[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 222AmmoniaHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867116834-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoic acid

生成物 1

HCID 733360134-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanamide収率 37.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoic acid (0.029 g, 0.08 mmol) and NH3 (0.3 mL, sat. in CH2Cl2) in DMF (0.6 mL) was added HATU (0.040 g, 0.10 mmol). The mixture was stirred at rt for 30 min. It was then quenched with water. The mixture was partitioned between IPA/CHCl3 (1:2, 50 mL) and sat. NaHCO3 (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo, and purified by reverse phase HPLC to afford the desired product (0.014 g, 37%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.42 (dd, J=9.2, 4.6 Hz, 2H), 7.16 (dd, J=8.4, 8.0 Hz, 2H), 6.53 (s, 1H), 6.34 (s, 1H), 6.32 (s, 1H), 5.92 (m, 1H), 3.80 (m, 1H), 3.41 (m, 1H), 3.33 (m, 1H), 3.00 (m, 1H), 2.76 (m, 2H), 2.37 (s, 3H), 1.98 (m, 1H), 1.88 (m, 1H); MS: (ES) m/z calculated for C21H20F4N6O2 [M+H]+ 465.1, found 465.1.

後処理

  1. customIt was then quenched with water
  2. customThe mixture was partitioned between IPA/CHCl3 (1:2, 50 mL) and sat. NaHCO3 (30 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-7ec8024e89f04a98bae39480ee25b261
出典データセット
uspto-grants-2015_11
特許番号
US09181241B2

反応ノート

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