2-Amino-5-bromopyridine → tert-Butyl {4-[5-(6-amino-pyridin-3-yl)-2-methoxy-benzylamino]-cyclohexyl}-methyl-carbamate

HRID 2389639Notes

Reaction equation

HRID 2389639 reaction equation
[C:1]([N:8]([CH3:28])[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][CH2:16][C:17]2[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:29][C:30]1[CH:35]=[CH:34][C:33](Br)=[CH:32][N:31]=1>Cl>[NH2:29][C:30]1[N:31]=[CH:32][C:33]([C:19]2[CH:20]=[CH:21][C:22]([O:23][CH3:24])=[C:17]([CH:18]=2)[CH2:16][NH:15][CH:12]2[CH2:13][CH2:14][CH:9]([N:8]([CH3:28])[C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH2:10][CH2:11]2)=[CH:34][CH:35]=1

Participants

4

Reactant 2

HCID 706222-Amino-5-bromopyridineHCID 252081913-{[4-(BOC-methyl-amino)-cyclohexylamino]-methyl}-4-methoxy-benzene boronic acid

Product 1

HCID 59683549tert-Butyl {4-[5-(6-amino-pyridin-3-yl)-2-methoxy-benzylamino]-cyclohexyl}-methyl-carbamate

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Boronic acid 4 (900 mg, 2.29 mmol) is coupled to 2-amino-5-bromopyridine (475 mg, 2.74 mmol) using Method A. On completion, the cooled reaction mixture is diluted with 1 M HCl (10 mL) and extracted with TBME (3×10 mL). The aqueous phase is then basified to pH 9 by careful addition of solid NaHCO3 and extracted into EtOAc (50 mL) and DCM (3×50 mL). The combined organic phases are dried over Na2SO4 and reduced in vacuo to yield the crude title product.

Workup

  1. customOn completion, the cooled reaction mixture
  2. extractionextracted with TBME (3×10 mL)
  3. additionThe aqueous phase is then basified to pH 9 by careful addition of solid NaHCO3
  4. extractionextracted into EtOAc (50 mL) and DCM (3×50 mL)
  5. dry with materialThe combined organic phases are dried over Na2SO4

Sources & evidence

ORD record
ord-14ac855a966242f48dfc3cc17f5ebd12
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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