Diethyl Ether → 4-{[(1S,2R)-2-aminocyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamide

HRID 75525Notes

Reaction equation

HRID 75525 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[N:17]=[C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]2[NH:25]C(=O)OC(C)(C)C)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:33])[CH:14]=2)[N:9]=1)=[O:7].C(OCC)(=O)C.Cl.C(OCC)C>C(OCC)(=O)C>[NH2:25][C@@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@@H:19]1[NH:18][C:16]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:33])[CH:14]=2)[N:9]=[C:8]([C:6]([NH:5][CH2:4][CH2:3][O:2][CH3:1])=[O:7])[N:17]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 21866389Hydrogen chloride-ethyl acetateHCID 86638400tert-butyl {(1R,2S)-2-[(2-{[(2-methoxyethyl)amino]carbonyl}-6-methylquinazolin-4-yl)amino]cyclohexyl}carbamate

Product 1

HCID 687002114-{[(1S,2R)-2-aminocyclohexyl]amino}-N-(2-methoxyethyl)-6-methylquinazolin-2-carboxamideYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2.24 g of tert-butyl {(1R,2S)-2-[(2-{[(2-methoxyethyl)amino]carbonyl}-6-methylquinazolin-4-yl)amino]cyclohexyl}carbamate in 10 ml of ethyl acetate, 10 ml of a 4 N hydrogen chloride-ethyl acetate solution was added, and the mixture was stirred at room temperature for 48 hours. To the reaction solution, 20 ml of diethyl ether was added, and the mixture was stirred for 30 minutes. Then, the deposited substance was collected by filtration, washed with diethyl ether and dried under reduced pressure. The resulting powder was purified by Fuji Silysia NH silica gel column chromatography (chloroform:methanol=20:1), whereby 1.61 g of a desired compound was obtained as a colorless powder.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 30 minutes
  3. filtrationThen, the deposited substance was collected by filtration
  4. washwashed with diethyl ether
  5. customdried under reduced pressure
  6. customThe resulting powder was purified by Fuji Silysia NH silica gel column chromatography (chloroform:methanol=20:1)

Sources & evidence

ORD record
ord-ccbe36490b6e44f4b12ab1b7f4b8d921
Source dataset
uspto-grants-2014_09
Patent number
US08835446B2

Reaction notes

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