1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 22995797, compound

HRID 1167168Notes

Reaction equation

HRID 1167168 reaction equation
N12CCCN=C1CCCCC2.[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:37][CH2:38][CH2:39]Br)=[C:28]([O:31][CH:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19].[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]>C(#N)C>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:37][CH2:38][CH2:39][N:51]4[CH2:50][CH2:49][N:48]([C:46]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:47])[CH2:53][CH2:52]4)=[C:28]([O:31][CH:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:29]=3)[N:24]=[CH:23][N:22]=2)[CH:16]=[CH:17][C:18]=1[F:19]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 143452tert-Butyl piperazine-1-carboxylate2×HCID 18762862HCID 18762862, compound

Product 1

HCID 22995797HCID 22995797, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

340 mg of 1,8-diazabicyclo[5.4.0]undec-7-ene are added at ambient temperature to 940 mg of 4-[(3-chloro-4-fluorophenyl)amino]-6-cyclopentyloxy-7-(2-bromoethoxy)-quinazoline and 1.00 g of N-(tert.butyloxycarbonyl)-piperazine in 30 ml of acetonitrile. The reaction mixture is heated to 60° C. for five hours. Then a further 0.2 g of N-(tert.butyloxycarbonyl)-piperazine and some 1,8-diazabicyclo[5.4.0]undec-7-ene are added. The yellow reaction solution is stirred for two hours at 60° C. and then overnight at ambient temperature, during which time a white precipitate is formed. This is suction filtered, washed with a little acetonitrile and dried. 453 mg of the desired product are obtained as a white solid. The mother liquor is concentrated by evaporation and the flask residue is chromatographed over a silica gel column with methylene chloride/methanol (95:5). Another 300 mg of the desired product are obtained.

Workup

  1. customovernight at ambient temperature, during which time a white precipitate is formed
  2. filtrationThis is suction filtered
  3. washwashed with a little acetonitrile
  4. customdried

Sources & evidence

ORD record
ord-dcbbce8f2c95408d9ab590aef2459dc7
Source dataset
uspto-grants-2003_09
Patent number
US06617329B2

Reaction notes

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