Cesium fluoride → [4-[6-Amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-2-(4-piperidyl)pyrazol-3-yl]methanol

HRID 908469ノート

反応式

HRID 908469 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([N:25](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:41]1[CH:42]=[N:43][N:44]([CH:48]2[CH2:53][CH2:52][N:51](C(OC(C)(C)C)=O)[CH2:50][CH2:49]2)[C:45]=1[CH2:46][OH:47].[F-].[Cs+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>[NH2:25][C:11]1[N:12]=[CH:13][C:14]([C:41]2[CH:42]=[N:43][N:44]([CH:48]3[CH2:49][CH2:50][NH:51][CH2:52][CH2:53]3)[C:45]=2[CH2:46][OH:47])=[CH:15][C:10]=1[C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

参加物

6

反応物 3

HCID 25953Cesium fluorideHCID 67388159Tert-butyl 4-(4-bromo-5-(hydroxymethyl)pyrazol-1-yl)piperidine-1-carboxylateHCID 67388208Tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate

生成物 1

HCID 57687096[4-[6-Amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-2-(4-piperidyl)pyrazol-3-yl]methanol収率 42.3%

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 887Methanol溶媒

反応条件

温度
120 °C

実験手順

Tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (250 mg), tert-butyl 4-(4-bromo-5-(hydroxymethyl)pyrazol-1-yl)piperidine-1-carboxylate (131 mg), bis(triphenylphosphine) palladium chloride (12.73 mg) and caesium fluoride (165 mg) were weighed out in a microwave vial and sealed. Methanol (3 ml) was added and argon was let to bubble in the resulting suspension for 5 minutes. The resulting mixture was heated in the microwave at 120° C. for 20 minutes. Insolubles were removed by filtration and the filtrate was concentrated. Hydrogen chloride (5N in isopropanol) (1.814 ml) was added and the mixture was heated at reflux for 2 hours. The resulting precipitate was collected by filtration, washed with isopropanol. The solid was taken up into methanolic ammonia (7N-2 mL) and dicalite speed plus. The crude product was purified by flash chromatography on silica gel eluting with 5 to 10% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford [4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-2-(4-piperidyl)pyrazol-3-yl]methanol (60 mg). NMR Spectrum: (DMSOd6) 1.80-1.89 (m, 2H), 1.93 (dd, 1H), 1.98 (dd, 1H), 2.25 (bs, 1H), 2.57-2.67 (m, 2H), 3.03-3.11 (m, 2H), 4.37-4.46 (m, 1H), 4.56 (d, 2H), 5.46 (t, 1H), 7.41-7.48 (m, 2H), 7.70 (bs, 2H), 7.71 (s, 1H), 7.79 (dd, 1H), 7.85 (dd, 1H), 8.35 (d, 1H), 8.36 (d, 1H). Mass spectrum: M+H+ 391;

後処理

  1. customsealed
  2. customto bubble in the resulting suspension for 5 minutes
  3. customInsolubles were removed by filtration
  4. concentrationthe filtrate was concentrated
  5. additionHydrogen chloride (5N in isopropanol) (1.814 ml) was added
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 2 hours
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with isopropanol
  10. customThe crude product was purified by flash chromatography on silica gel eluting with 5 to 10% methanolic ammonia (7 N) in dichloromethane
  11. customThe solvent was evaporated to dryness

出典と根拠

ORDレコード
ord-9b8ae386029047ebaaaf01e883721aa2
出典データセット
uspto-grants-2011_09
特許番号
US08017611B2

反応ノート

読み込み中…