Water → 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile

HRID 1848132ノート

反応式

HRID 1848132 の反応式
Br[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[O:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.O.[CH3:30][N:31](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[OH:26][C@@H:21]1[CH2:22][CH2:23][CH2:24][CH2:25][C@H:20]1[NH:19][C:17]1[O:18][C:14]2[CH:13]=[C:12]([CH2:11][N:8]3[C:5]4=[N:6][CH:7]=[C:2]([C:30]#[N:31])[CH:3]=[C:4]4[N:10]=[CH:9]3)[CH:28]=[CH:27][C:15]=2[N:16]=1

参加物

7

反応物 3

HCID 962WaterHCID 6228DimethylformamideHCID 71549859(1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

生成物 1

HCID 866811013-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile収率 25.8%

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
100 °C

実験手順

A mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (276 mg, 0.62 mmol), Zn(CN)2 (110 mg, 0.94 mmol), Pd2(dba)3 (57 mg, 0.062 mmol) and dppf (68.8 mg, 0.124 mmol) in DMF (6 mL) was stirred at 100° C. for 2 h. The reaction mixture was cooled to rt, poured into water (100 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 15:1 DCM/MeOH to give 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile as a light yellow solid (62 mg, 25.8%). 1H NMR (300 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.83 (d, J=1.5 Hz, 1H), 8.70 (s, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.41 (s, 1H), 7.14 (m, 2H), 5.54 (s, 2H), 4.68 (d, J=4.8 Hz, 1H), 3.34 (br s, 2H), 1.91 (br s, 2H), 1.62 (br s, 2H), 1.22 (br, 4H). LCMS (ESI) m/z 389 (M+H)+.

後処理

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (100 mL×2)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 15:1 DCM/MeOH

出典と根拠

ORDレコード
ord-9934456ad094415797e1b0914f0457f6
出典データセット
uspto-grants-2015_02
特許番号
US08952058B2

反応ノート

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