Calcium Carbonate → diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoyl}-L-glutamate

HRID 1289228

反応式

HRID 1289228 の反応式
Br[CH:2]1[C:6]2[CH:7]=[C:8]3[C:13](=[CH:14][C:5]=2[CH2:4][CH2:3]1)[N:12]=[C:11]([CH3:15])[N:10]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:9]3=[O:24].[NH2:25][C:26]1[CH:47]=[CH:46][C:29]([C:30]([NH:32][C@H:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[O:31])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Ca+2]>CC(N(C)C)=O>[CH3:15][C:11]1[N:10]([CH2:16][O:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C:9](=[O:24])[C:8]2[C:13](=[CH:14][C:5]3[CH2:4][CH2:3][CH:2]([NH:25][C:26]4[CH:27]=[CH:28][C:29]([C:30]([NH:32][C@H:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[O:31])=[CH:46][CH:47]=4)[C:6]=3[CH:7]=2)[N:12]=1

参加物

5

反応物 3

HCID 10112Calcium CarbonateHCID 73002Diethyl N-(4-aminobenzoyl)-L-glutamateHCID 105246016-bromo-2-methyl-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4-one2 回

生成物 1

HCID 10532105diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoyl}-L-glutamate

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
110 °C

実験手順

A mixture of 6-bromo-2-methyl-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4-one (21 g), prepared as described in section (6) of Example 1, diethyl p-aminobenzoyl-L-glutamate (52.5 g), prepared as described in the Journal of Medicinal Chemistry, 1985, 28, 1428, calcium carbonate (27.5 g) and DMA (200 ml) was stirred and heated to 110° C. for 30 minutes. The mixture was cooled to ambient temperature. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was purified by column chromatography using initially a 1:1 mixture of hexane and ethyl acetate as eluant and then a 1:3 mixture of hexane and ethyl acetate as eluant. There was thus obtained a gum which on trituration under diethyl ether gave diethyl N-{(p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzoyl}-L-glutamate (13.5 g), m.p. 156° C.;

後処理

  1. customprepared
  2. customprepared
  3. temperatureThe mixture was cooled to ambient temperature
  4. customThe mixture was evaporated
  5. customthe residue was partitioned between ethyl acetate and water
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by column chromatography
  9. additiona 1:1 mixture of hexane and ethyl acetate as eluant
  10. additiona 1:3 mixture of hexane and ethyl acetate as eluant
  11. customThere was thus obtained a gum which on trituration under diethyl ether
  12. customgave diethyl N-{(p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzoyl}-L-glutamate (13.5 g), m.p. 156° C.

出典と根拠

ORDレコード
ord-3c09bd3bfcda4e118da3219b9914899e
出典データセット
uspto-grants-1998_05
特許番号
US05747499

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