Calciumoxide → HCID 178507834, compound

HRID 1635060Notes

Reaction equation

HRID 1635060 reaction equation
[NH2:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([C:12]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][NH:24][C:25]3[NH:26][CH:27]=[CH:28][C:29](=[O:31])[N:30]=3)[CH2:18][CH2:17]2)=[O:13])=[CH:4][C:3]=1[Cl:32].ClC1N=C(O)[C:41]2[C:36](=[CH:37][CH:38]=CC=2)N=1.[O-2].[Ca+2]>CN(C)C(=O)C>[NH2:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]([C:12]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][NH:24][C:25]3[NH:26][C:27]4[C:28]([C:29](=[O:31])[N:30]=3)=[CH:38][CH:37]=[CH:36][CH:41]=4)[CH2:18][CH2:17]2)=[O:13])=[CH:4][C:3]=1[Cl:32]

Participants

5

Reactant 3

HCID 6850728CalciumoxideHCID 178507835HCID 178507835, compoundHCID 178517815HCID 178517815, compound

Product 1

HCID 178507834HCID 178507834, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of intermediate 15 (2 g), 2-chloro-4-hydroxyquinazoline (1.9 g), N,N-dimethylacetamide (0.3 ml) and calciumoxide (0.4 g) was stirred for 1 hour at 140° C., then cooled and partitioned between water and DCM (+methanol). The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The desired fractions were collected and the solvent was evaporated. The residue was suspended in DIPE, filtered off, then dried (vacuum, 60° C.), yielding 1.4 g (50%) [1-[2-[(1,4-dihydro-4-oxo-2-quinazolinyl)amino]ethyl]-4-piperidinyl]methyl 8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-carboxylate (compound 19).

Workup

  1. temperaturecooled
  2. custompartitioned between water and DCM (+methanol)
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5)
  8. customThe desired fractions were collected
  9. customthe solvent was evaporated
  10. filtrationfiltered off
  11. customdried (vacuum, 60° C.)

Sources & evidence

ORD record
ord-4c53c11c64b94f168f38badf38379cc1
Source dataset
uspto-grants-2003_01
Patent number
US06509339B2

Reaction notes

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