Nitrogen → Ammonia

HRID 1524192노트

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HRID 1524192 반응식
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

참가 물질

9

반응물 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]pyridine2회

생성물 2

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매2회

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온도
85 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3655ddf336a3491fa1fb4684e4496b1e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079897B2

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