Nitrogen → Ammonia

HRID 1524192ノート

反応式

HRID 1524192 の反応式
Br[C:2]1[N:7]=[C:6]2[N:8]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([Cl:17])[CH:12]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.N#N.[NH2:66][CH:67]1[CH2:72][CH2:71][CH:70]([OH:73])[CH2:69][CH2:68]1.CC(C)([O-])C.[Na+]>O1CCOCC1.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]>[NH3:7].[Cl:17][C:13]1[CH:12]=[C:11]([N:8]2[C:6]3=[N:7][C:2]([NH:66][CH:67]4[CH2:72][CH2:71][CH:70]([OH:73])[CH2:69][CH2:68]4)=[CH:3][CH:4]=[C:5]3[N:10]=[CH:9]2)[CH:16]=[CH:15][N:14]=1

参加物

9

反応物 5

HCID 947NitrogenHCID 812934-AminocyclohexanolHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 866518705-bromo-3-(2-chloro-pyridin-4-yl)-3-H-imidazo[4,5-b]pyridine2 回

生成物 2

HCID 222AmmoniaHCID 866518694-[3-(2-Chloro-pyridin-4-yl)-3H-imidazo[4,5-b]pyridine-5-ylamino]-cyclohexanol

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
85 °C

実験手順

A mixture comprising 5-bromo-3-(2-chloro-pyridin-4-yl)-3-H-imidazo[4,5-b]pyridine (Intermediate A)(1 eq, 0.323 mmol, 100 mg), BINAP (0.025 mmol, 40 mg) and Pd2(dba)3 (0.0125 mmol, 25 mg) is suspended in dioxane under an inert atmosphere of N2 and heated to 85° C. In a separate flask 4-amino-cyclohexanol (2 eq, 0.647 mmol, 74 mg) and sodium tertbutoxide (2.5 eq, 0.809 mmol, 77 mg) is dissolved in dioxane and warmed to 50° C., before adding to the reaction mixture. The combined mixture was heated for 2 hours. After cooling to room temperature, the mixture is purified by chromatography on silica eluting with 98:2 DCM: ammonia in MeOH to afford the title compound which is used in the next step without further purification; [M+H]+310.

後処理

  1. temperaturewarmed to 50° C.
  2. additionbefore adding to the reaction mixture
  3. temperatureThe combined mixture was heated for 2 hours
  4. temperatureAfter cooling to room temperature
  5. customthe mixture is purified by chromatography on silica eluting with 98:2 DCM

出典と根拠

ORDレコード
ord-3655ddf336a3491fa1fb4684e4496b1e
出典データセット
uspto-grants-2015_07
特許番号
US09079897B2

反応ノート

読み込み中…