6-(BOC-amino)-3-azabicyclo[3.1.0]hexane → [6-(6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine

HRID 584564Notes

Reaction equation

HRID 584564 reaction equation
F[C:2]1[N:26]=[CH:25][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=4)=[C:13]([CH3:24])[CH:12]=3)[C:4]=2[CH:3]=1.C(OC(=O)[NH:33][CH:34]1[CH:39]2[CH:35]1[CH2:36][NH:37][CH2:38]2)(C)(C)C>C(O)C.C(Cl)(Cl)Cl>[NH2:33][CH:34]1[CH:39]2[CH:35]1[CH2:36][N:37]([C:2]1[N:26]=[CH:25][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([O:17][C:18]5[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=5)=[C:13]([CH3:24])[CH:12]=4)[C:4]=3[CH:3]=1)[CH2:38]2

Participants

5

Reactant 2

HCID 111483086-(BOC-amino)-3-azabicyclo[3.1.0]hexaneHCID 11405275(6-Fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine

Product 1

HCID 10224262[6-(6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amineYield 53.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Procedure

A solution of 2.71 g (7.83 mmol) of (6-fluoro-pyrido[3,4-d]pyrimidin-4-yl)-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine and 31.0 g (156.5 mmol) of (3-aza-bicyclo[3.1.0]hex-6-yl)-carbamic acid tert-butyl ester in 20 mL of ethanol in a sealed tube was heated at 105° C. for 24 hours. The mixture was cooled to room temperature and diluted with chloroform. The organics were washed sequentially with 3×150 mL saturated sodium bicarbonate and 1×50 mL of saturated sodium chloride, dried over sodium sulfate and evaporated. Chromatography over silica gel, eluting with 5% methanol/chloroform afforded 1.79 g (43%) of the title compound. 1H NMR (CDCl3): δ 8.93 (s, 1), 8.53 (s, 1), 8.33 (m, 2), 7.60 (m, 3), 7.21 (m, 2), 6.96 (d, 1), 6.24 (m, 1), 4.83 (m, 1), 3.81 (m, 2), 3.51 (m, 2), 3.47 (m, 1), 2.36 (m, 1), 2.26 (s, 3), 1.88 (m, 1).

Workup

  1. washThe organics were washed sequentially with 3×150 mL saturated sodium bicarbonate and 1×50 mL of saturated sodium chloride
  2. dry with materialdried over sodium sulfate
  3. customevaporated
  4. washChromatography over silica gel, eluting with 5% methanol/chloroform

Sources & evidence

ORD record
ord-8b2e5677fae2404998b015b740086fc2
Source dataset
uspto-grants-2005_08
Patent number
US06927220B2

Reaction notes

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