Nitrogen → Ammonia

HRID 1524194Notes

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:64]#N.N[CH:67]1[CH2:72][CH2:71][CH2:70][CH:69]([OH:73])[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]([CH:70]4[CH2:71][CH2:72][CH2:67][CH2:68][C:69]4([NH2:64])[OH:73])=[CH:3][CH:4]=[C:5]3[N:10]=[CH:9]2)[CH:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 85 °C

Procedure

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) are suspended in dioxane under an inert atmosphere of N2 and heated to 85° C. In a separate flask (1SR,3SR)-3-aminocyclohexanol (2 eq, 0.647 mmol, 83 mg) and sodium tertbutoxide (2.5 eq, 0.809 mmol, 77 mg) is dissolved in dioxane and warmed to 50° C. Once at temperature mixture is added to the reaction mixture and heated for 2 hours. After cooling to room temperature, the mixture is purified by chromatography on silica eluting with 98:2 DCM: 2M ammonia in MeOH to afford the title compound which is used in the next step without further purification; [M+H]+ 310.

Workup

temperaturewarmed to 50° C
additionOnce at temperature mixture is added to the reaction mixture
temperatureheated for 2 hours
temperatureAfter cooling to room temperature
customthe mixture is purified by chromatography on silica eluting with 98:2 DCM

Sources & evidence

ORD record: ord-b1f7c538022b4ae696958ca6023e5bce
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079897B2

Reaction notes

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