2-Fluoroethanol → HCID 178424913、化合物

HRID 80852

反応式

HRID 80852 の反応式
Cl[C:2]1[C:3]2[CH2:24][N:23]([C:25]3[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[CH:28]=[CH:27][C:26]=3[CH3:34])[CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([C:8]2[C:16]([CH3:17])=[CH:15][CH:14]=[C:13]3[C:9]=2[C:10]([CH3:20])=[N:11][N:12]3C=O)[N:7]=1.[F:35][CH2:36][CH2:37][OH:38].[H-].[Na+]>C1COCC1>[CH3:20][C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:17])[C:8]=2[C:6]2[N:7]=[C:2]([O:38][CH2:37][CH2:36][F:35])[C:3]3[CH2:24][N:23]([C:25]4[CH:30]=[C:29]([CH:31]([CH3:32])[CH3:33])[CH:28]=[CH:27][C:26]=4[CH3:34])[CH2:22][CH2:21][C:4]=3[N:5]=2)[NH:12][N:11]=1

参加物

5

反応物 3

HCID 97372-FluoroethanolHCID 24758Sodium hydrideHCID 866902884-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde

生成物 1

HCID 178424913HCID 178424913、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-(4-chloro-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)-3,5-dimethyl-1H-indazole-1-carbaldehyde (30 mg, 0.063 mmol) in THF (3 mL) was added 2-fluoroethanol (16.2 mg, 0.25 mmol) and NaH (15.1 mg, 0.63 mmol, 60% in mineral oil). The mixture was stirred at room temperature for 4 h. LC-MS showed reaction complete. The reaction mixture was concentrated and the residue was partitioned between saturated aqueous NH4Cl solution and DCM. The layers were separated and the aqueous layer was extracted further with DCM. The organics were combined and concentrated. The residue was purified by FCC (0-100% EtOAc/heptane) to provide 2-(3,5-dimethyl-1H-indazol-4-yl)-4-(2-fluoroethoxy)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.47 (d, J=8.59 Hz, 1H), 7.34 (s, 1H), 7.15 (d, J=7.71 Hz, 1H), 7.06 (d, J=1.39 Hz, 1H), 6.92 (dd, J=1.52, 7.71 Hz, 1H), 4.71-4.81 (m, 2H), 4.67 (s, 2H), 4.13 (s, 2H), 3.33-3.39 (m, 2H), 3.05 (t, J=5.56 Hz, 2H), 2.88 (td, J=6.93, 13.80 Hz, 1H), 2.32 (s, 3H), 2.27 (s, 3H), 1.98 (s, 3H), 1.25 (d, J=6.82 Hz, 6H); MS (ESE) m/z 474.4 (M+H)+.

後処理

  1. customreaction complete
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between saturated aqueous NH4Cl solution and DCM
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted further with DCM
  6. concentrationconcentrated
  7. customThe residue was purified by FCC (0-100% EtOAc/heptane)

出典と根拠

ORDレコード
ord-04b0c18196cf48118e1f05072d283ab4
出典データセット
uspto-grants-2014_09
特許番号
US08846656B2

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