Calciumoxide → HCID 178422917, compound

HRID 1488447Notes

Reaction equation

HRID 1488447 reaction equation
Cl[C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=2)[N:3]=1.[NH2:14][C:15]1[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[C:18]([C:26]([NH:28][CH:29]2[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][NH2:37])[CH2:31][CH2:30]2)=[O:27])=[CH:17][C:16]=1[Cl:38].[O-2].[Ca+2]>CN(C)C(=O)C>[NH2:14][C:15]1[C:20]2[CH2:21][C:22]([CH3:24])([CH3:25])[O:23][C:19]=2[C:18]([C:26]([NH:28][CH:29]2[CH2:30][CH2:31][N:32]([CH2:35][CH2:36][NH:37][C:2]3[N:11]=[C:10]([OH:12])[C:9]4[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=4)[N:3]=3)[CH2:33][CH2:34]2)=[O:27])=[CH:17][C:16]=1[Cl:38]

Participants

5

Reactant 3

HCID 6850728CalciumoxideHCID 54341646HCID 54341646, compoundHCID 178517817HCID 178517817, compound

Product 1

HCID 178422917HCID 178422917, compoundYield 18.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2.6 g of 2,6-dichloro-4-quinazolinol (described in J. Med. Chem., 1968, p.130), 3.7 g of 4-amino-N-[1-(2-aminoethyl)-4-piperidinyl]-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxamide (described in EP-0,445,862), 0.8 g of calcium oxide and 5.64 g of N,N-dimethylacetamide was stirred for 3 hours at 140° C. After cooling, the reaction mixture was evaporated and the residue was taken up in a mixture of dichloromethane and methanol. The whole was washed with water. The partly precipitated product was filtered off (first fraction). The organic layer was decanted, dried, filtered and evaporated (second fraction). The combined fractions were purified twice by column chromatography (silica gel; CH2Cl2 /CH3 OH(NH3) 95:5; CH2Cl2 /CH3OH 92:8). The eluent of the desired fraction was evaporated and the residue was crystallized from acetonitrile. At 0° C., the product was filtered off and dried in vacuo at 60° C., yielding 1 g (18.3%) of 4-amino-5-chloro-N-[1-[2-[(6-chloro-4-hydroxy-2-quinazolinyl)amino]ethyl]-4-piperidinyl]-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxamide; mp. 206.6° C. (comp. 21).

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was evaporated
  3. additionthe residue was taken up in a mixture of dichloromethane and methanol
  4. washThe whole was washed with water
  5. filtrationThe partly precipitated product was filtered off (first fraction)
  6. customThe organic layer was decanted
  7. customdried
  8. filtrationfiltered
  9. customevaporated (second fraction)
  10. customThe combined fractions were purified twice by column chromatography (silica gel; CH2Cl2 /CH3 OH(NH3) 95:5; CH2Cl2 /CH3OH 92:8)
  11. customThe eluent of the desired fraction was evaporated
  12. customthe residue was crystallized from acetonitrile
  13. filtrationAt 0° C., the product was filtered off
  14. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-4924e8a78db34806860529a0981e3891
Source dataset
uspto-grants-1997_10
Patent number
US05674868

Reaction notes

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