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

반응식

HRID 1289228 반응식
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

참가 물질

5

반응물 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-one2회

생성물 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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
110 °C

실험 절차

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.;

후처리

  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.

출처 및 근거

ORD 기록
ord-3c09bd3bfcda4e118da3219b9914899e
출처 데이터셋
uspto-grants-1998_05
특허 번호
US05747499

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