Calciumoxide → HCID 178422916, compound

HRID 1488446Notes

Reaction equation

HRID 1488446 reaction equation
Cl[C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:13][C:14]1[C:19]2[CH2:20][C:21]([CH3:24])([CH3:23])[O:22][C:18]=2[C:17]([C:25]([NH:27][CH:28]2[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][NH2:37])[CH2:30][CH2:29]2)=[O:26])=[CH:16][C:15]=1[Cl:38].[O-2].[Ca+2]>ClCCl.CO>[NH2:13][C:14]1[C:19]2[CH2:20][C:21]([CH3:23])([CH3:24])[O:22][C:18]=2[C:17]([C:25]([NH:27][CH:28]2[CH2:29][CH2:30][N:31]([CH2:34][CH2:35][CH2:36][NH:37][C:2]3[N:11]=[C:10]([OH:12])[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=3)[CH2:32][CH2:33]2)=[O:26])=[CH:16][C:15]=1[Cl:38]

Participants

6

Reactant 3

HCID 6850728CalciumoxideHCID 54219572HCID 54219572, compoundHCID 178517815HCID 178517815, compound

Product 1

HCID 178422916HCID 178422916, compoundYield 50.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4.15 g of 2-chloro-4-hydroxyquinazoline, 4.57 g of 4-amino-N-[1-(3-aminopropyl)-4-piperidinyl]-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxamide (described in EP-0,445,862) and 0.80 g of calcium oxide was stirred for 1 hour at 140° C. The reaction mixture was dissolved in a mixture of dichloromethane and methanol. The whole was washed with water, dried, filtered and evaporated. The residue was purified twice by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 90:10; CH2Cl2 /CH3OH(NH3) 88:12). The eluent of the desired fraction was evaporated and the residue was boiled in 2,2'-oxybispropane. The product was filtered off and dried, yielding 3.2 g (50.8%) of 4-amino-5-chloro-2,3-dihydro-N-[1-[3-[(4-hydroxy-2-quinazolinyl)amino]propyl]-4-piperidinyl]-2,2-dimethyl-7-benzofurancarboxamide; mp. 159.6° C. (comp. 12).

Workup

  1. washThe whole was washed with water
  2. customdried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified twice by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 90:10; CH2Cl2 /CH3OH(NH3) 88:12)
  6. customThe eluent of the desired fraction was evaporated
  7. filtrationThe product was filtered off
  8. customdried

Sources & evidence

ORD record
ord-da135b4f7cf44809981b0e9db83d9b69
Source dataset
uspto-grants-1997_10
Patent number
US05674868

Reaction notes

Loading…