Triphenylphosphine dibromide → Tert-butyl 3-(5-(3-amino-6-bromopyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzylcarbamate

HRID 78635

反応式

HRID 78635 の反応式
[NH2:1][C:2]1[C:3]([C:9]([NH:11][NH2:12])=[O:10])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:35]([O:39][C:40]([NH:42][CH2:43][C:44]1[CH:45]=[C:46]([CH:50]=[CH:51][CH:52]=1)[C:47](O)=O)=[O:41])([CH3:38])([CH3:37])[CH3:36].CCN(C(C)C)C(C)C.BrP(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:3]([C:9]2[O:10][C:47]([C:46]3[CH:45]=[C:44]([CH:52]=[CH:51][CH:50]=3)[CH2:43][NH:42][C:40](=[O:41])[O:39][C:35]([CH3:38])([CH3:36])[CH3:37])=[N:12][N:11]=2)=[N:4][C:5]([Br:8])=[CH:6][N:7]=1

参加物

8

反応物 5

HCID 70579Triphenylphosphine dibromideHCID 81531Diisopropylethylamine2 回HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27559293-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 580702563-Amino-6-bromopyrazine-2-carbohydrazide

生成物 1

HCID 59471784Tert-butyl 3-(5-(3-amino-6-bromopyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzylcarbamate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

3-amino-6-bromo-pyrazine-2-carbohydrazide (1.2 g, 5.172 mmol), TBTU (1.333 g, 5.689 mmol), 3-[(tert-butoxycarbonylamino)methyl]benzoic acid (1.300 g, 5.172 mmol) and DIPEA (1.338 g, 1.803 mL, 10.35 mmol) in a solution in DMF (13.98 mL) were stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate (35 mL), washed with water (2×50 mL) and brine (1×50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to a solid. This solid was suspended in MeCN (83.89 mL) at room temperature followed by the addition of dibromo(triphenyl)phosphorane (2.183 g, 5.172 mmol) and DIPEA (1.338 g, 1.803 mL, 10.35 mmol). The resulting mixture was stirred at room temperature for 2 h and then concentrated in vacuo to leave a solid. This was purified by column chromatography on silica eluting with EtOAc/petroleum ether, Product fractions were combined and concentrated in vacuo to leave the product as a white solid. The mixture was conc. to a solid and purified by column chromatography using ethylacetate/pet ether as elaunt to afford the product as a white solid (924 mg, 40% yield); 1H NMR (400 MHz, DMSO) d 1.43 (s, 9H), 4.26 (m, 2H), 7.55 (m, 3H), 7.80 (br s, 2H), 7.97 (m, 1H) and 8.45 (s, 1H) ppm; MS (ES+) 449.08

後処理

  1. washwashed with water (2×50 mL) and brine (1×50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo to a solid
  4. customwas suspended in MeCN (83.89 mL) at room temperature
  5. concentrationconcentrated in vacuo
  6. customto leave a solid
  7. customThis was purified by column chromatography on silica eluting with EtOAc/petroleum ether, Product fractions
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ee8b6b328d194823ae21e5f704f661da
出典データセット
uspto-grants-2014_09
特許番号
US08841308B2

関連ノート

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