Sodium hydride → (1S,4R)-4-[3-(2,6-Dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 75613ノート

反応式

HRID 75613 の反応式
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=1[C:23]1[N:27]2[CH:28]=[C:29](F)[CH:30]=[CH:31][C:26]2=[N:25][N:24]=1>CN(C=O)C>[Cl:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[C:17]=1[C:23]1[N:27]2[CH:28]=[C:29]([O:12][C@H:5]3[C:6]4[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=4)[C@@H:2]([NH2:1])[CH2:3][CH2:4]3)[CH:30]=[CH:31][C:26]2=[N:25][N:24]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 848195623-(2,6-Dichlorophenyl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-ol

生成物 1

HCID 86686715(1S,4R)-4-[3-(2,6-Dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine収率 33%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Intermediate 1d (404 mg, 2.48 mmol) was added to a stirred solution of sodium hydride (60% in mineral oil, 298 mg, 7.44 mmol) in anhydrous DMF (15 mL) at RT under an argon atmosphere. The reaction mixture was stirred at RT for 15 min, then Intermediate 26c (0.70 g, 2.48 mmol) was added, and stirring at 60° C. was continued for 1 h. After cooling, the reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1) and extracted with EtOAc (×3). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 followed by brine, dried and concentrated in vacuo. The resultant residue was purified by FCC, using 0-20% [2M NH3 in MeOH] in DCM to afford the title compound (345 mg, 33%) as a brown residue. LCMS (Method 3): Rt 2.34 min, m/z 425, 427. [MH+].

後処理

  1. stirringstirring at 60° C.
  2. waitwas continued for 1 h
  3. temperatureAfter cooling
  4. customthe reaction mixture was quenched by careful addition of a saturated aqueous solution of NH4Cl and water (1:1)
  5. extractionextracted with EtOAc (×3)
  6. washThe combined organic layers were washed with a saturated aqueous solution of NaHCO3
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by FCC

出典と根拠

ORDレコード
ord-6a27d97f64b1499f8e276f9938dc5c41
出典データセット
uspto-grants-2014_09
特許番号
US08835431B2

反応ノート

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