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Nitrogen → Ammonia

HRID 1524192
Notes
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Reaction equation

HRID 1524192 reaction equation
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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 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×

Product 2

HCID 222Ammonia
HCID 86651869
4-[3-(2-Chloro-pyridin-4-yl)-3H-imidazo[4,5-b]pyridine-5-ylamino]-cyclohexanol

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3655ddf336a3491fa1fb4684e4496b1e
Source dataset
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09079897B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes