Water → HCID 11785508, compound

HRID 993159Notes

Reaction equation

HRID 993159 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3[C:32]4[C:27](=[CH:28][C:29]([NH:36][CH2:37][CH3:38])=[C:30]([N+:33]([O-])=O)[CH:31]=4)[N:26]=[CH:25][N:24]=3)[CH2:19][CH2:18]2)=[O:16])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H].[C:41](N1C=CN=C1)(N1C=CN=C1)=[O:42].O>C(O)C.[C].[Pd]>[CH2:37]([N:36]1[C:29]2[C:30](=[CH:31][C:32]3[C:23]([N:20]4[CH2:21][CH2:22][N:17]([C:15]([NH:14][C:11]5[CH:12]=[CH:13][C:8]([O:1][C:2]6[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=6)=[CH:9][CH:10]=5)=[O:16])[CH2:18][CH2:19]4)=[N:24][CH:25]=[N:26][C:27]=3[CH:28]=2)[NH:33][C:41]1=[O:42])[CH3:38]

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 11249274HCID 11249274, compound2×HCID 178418361HCID 178418361, compound

Product 1

HCID 11785508HCID 11785508, compoundYield 34.2%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 197.5 mg (0.38 mmol) of N-(4-phenoxyphenyl)-4-(7-ethylamino-6-nitro-4-quinazolinyl)-1-piperazinecarboxamide (Compound 109) obtained in Example 109 in 4 ml of ethanol was added 30 mg of 10% palladium-carbon, followed by stirring for 7.5 hours in a stream of hydrogen. The catalyst was separated by filtration with Celite and the solvent was evaporated. The obtained residue was dissolved in 10 ml of dimethylformamide, and 187.2 mg (1.15 mmol) of carbonyldiimidazole was added thereto, followed by stirring at 80° C. for 2 hours in an atmosphere of argon. After the reaction mixture was poured into water, the precipitated crystals were collected by filtration, washed with water, and dried, followed by purification by silica gel column chromatography to give 65.7 mg (0.13 mmol) of the desired compound as colorless crystals.

Workup

  1. customThe catalyst was separated by filtration with Celite
  2. customthe solvent was evaporated
  3. dissolutionThe obtained residue was dissolved in 10 ml of dimethylformamide
  4. filtrationthe precipitated crystals were collected by filtration
  5. washwashed with water
  6. customdried
  7. customfollowed by purification by silica gel column chromatography

Sources & evidence

ORD record
ord-3f619bd424e548dfa29aad408cbd3dd9
Source dataset
uspto-grants-2002_10
Patent number
US06472391B2

Reaction notes

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