Triethylamine → 4-[(3-chloro-4-fluorophenyl)amino]-6-cyclopentylmethoxy-7-(2-{4-[(S)-(2-oxo-tetrahydrofuran-5-yl)carbonyl]-piperazin-1-yl}-ethoxy)-quinazoline

HRID 1167170

Reaction equation

HRID 1167170 reaction equation
[O:1]=[C:2]1[O:6][C@H:5]([C:7]([OH:9])=O)[CH2:4][CH2:3]1.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.F[B-](F)(F)F.[Cl:32][C:33]1[CH:34]=[C:35]([NH:40][C:41]2[C:50]3[C:45](=[CH:46][C:47]([O:58][CH2:59][CH2:60][N:61]4[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]4)=[C:48]([O:51][CH2:52][CH:53]4[CH2:57][CH2:56][CH2:55][CH2:54]4)[CH:49]=3)[N:44]=[CH:43][N:42]=2)[CH:36]=[CH:37][C:38]=1[F:39].C(N(CC)CC)C>CN(C)C=O.O>[Cl:32][C:33]1[CH:34]=[C:35]([NH:40][C:41]2[C:50]3[C:45](=[CH:46][C:47]([O:58][CH2:59][CH2:60][N:61]4[CH2:62][CH2:63][N:64]([C:7]([C@H:5]5[O:6][C:2](=[O:1])[CH2:3][CH2:4]5)=[O:9])[CH2:65][CH2:66]4)=[C:48]([O:51][CH2:52][CH:53]4[CH2:54][CH2:55][CH2:56][CH2:57]4)[CH:49]=3)[N:44]=[CH:43][N:42]=2)[CH:36]=[CH:37][C:38]=1[F:39]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 636468(2S)-5-oxooxolane-2-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 155471684-[(3-Chloro-4-fluorophenyl)amino]-6-cyclopentylmethoxy-7-[2-(piperazin-1-yl)-ethoxy]-quinazoline

Product 1

HCID 155471674-[(3-chloro-4-fluorophenyl)amino]-6-cyclopentylmethoxy-7-(2-{4-[(S)-(2-oxo-tetrahydrofuran-5-yl)carbonyl]-piperazin-1-yl}-ethoxy)-quinazoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

72 mg of (S)-(+)-5-oxo-tetrahydrofuran-2-carboxylic acid are dissolved in 2.5 ml of N,N-dimethylformamide, combined with 183 mg of (benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium-tetrafluoroborate and stirred for 30 minutes at ambient temperature. This solution is then added to a mixture of 250 mg of 4-[(3-chloro-4-fluorophenyl)amino]-6-cyclopentylmethoxy-7-[2-(piperazin-1-yl)-ethoxy]-quinazoline and 110 μl of triethylamine in 2.5 ml of N,N-dimethylformamide. The reaction mixture is stirred for five hours at ambient temperature. For working up the mixture is poured onto 50 ml of water. A white precipitate is formed, which is suction filtered and washed with water. The crude product is purified by chromatography over an Alox column (activity stage III) with methylene chloride/methanol (98:2) as eluant. The desired product is obtained as a light-coloured solid.

Workup

  1. stirringThe reaction mixture is stirred for five hours at ambient temperature
  2. customA white precipitate is formed
  3. filtrationfiltered
  4. washwashed with water
  5. customThe crude product is purified by chromatography over an Alox column (activity stage III) with methylene chloride/methanol (98:2) as eluant

Sources & evidence

ORD record
ord-8ecf5089882d4a92908b45181c6f4ce1
Source dataset
uspto-grants-2003_09
Patent number
US06617329B2

Linked notes

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