Diethyl N-(4-aminobenzoyl)-L-glutamate → Diethyl N-[4-[(2,4-diaminopyrido[2,3-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate

HRID 1388498

반응식

HRID 1388498 반응식
[NH2:1][C:2]1[N:3]=[C:4]([NH2:14])[C:5]2[CH:11]=[C:10]([CH:12]=O)[CH:9]=[N:8][C:6]=2[N:7]=1.[NH2:15][C:16]1[CH:37]=[CH:36][C:19]([C:20]([NH:22][C@H:23]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:21])=[CH:18][CH:17]=1>C(O)(=O)C.[Ni]>[NH2:1][C:2]1[N:3]=[C:4]([NH2:14])[C:5]2[CH:11]=[C:10]([CH2:12][NH:15][C:16]3[CH:17]=[CH:18][C:19]([C:20]([NH:22][C@H:23]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:21])=[CH:36][CH:37]=3)[CH:9]=[N:8][C:6]=2[N:7]=1

참가 물질

5

반응물 2

HCID 73002Diethyl N-(4-aminobenzoyl)-L-glutamateHCID 10726310Pyrido[2,3-d]pyrimidine-6-carboxaldehyde, 2,4-diamino-

생성물 1

HCID 12908481Diethyl N-[4-[(2,4-diaminopyrido[2,3-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate

시약·촉매·용매 2

HCID 935Nickel촉매HCID 176Acetic Acid용매

실험 절차

A solution of compound III (1.47 g, 5.90 mmol) in warm 70% acetic acid (59 ml) was cooled to 25° C., treated with diethyl p-aminobenzoyl-L-glutamate (2.28 g, 7.08 mmol) and hydrogenated in the presence of Raney nickel (6.3 g, weighed wet) at 25° C. and atmospheric pressure for 17 hours. The mixture was filtered and the catalyst was washed with 70% acetic acid (25 ml). The combined filtrate and wash was evaporated to dryness under high vacuum, and a solution of the residue in ethanol was filtered into 2 N Na2CO3 (60 ml). The mixture was stirred to give a homogeneous powder which was collected, washed with water and dried. A solution of the resultant powder in boiling ethanol (415 ml) was filtered hot and evaporated to dryness in vacuo. The residue was triturated with CHCl3 (85 ml), collected by filtration and the solid was washed with additional CHCl3 (40 ml). A suspension of the solid in boiling ethanol (140 ml) was stirred for 20 minutes and refrigerated. The product was collected by filtration and dried in vacuo (P2O5): yield 945 mg (32%), mp 262° C. (Kofler Heizbank). Mass spectrum, m/e 496 (M+1)+ ; λmax nm (ε×10-3); 0.1 N HCl --218 (42.4), 280 sh (19.3), 300 (22.0); pH 7--218 (36.4), 249 (20.2), 280 sh (22.3), 297 (23.6), 355 sh (6.10); 0.1 N NaOH --249 (22.0), 280 (23.8), 297 sh (22.5), 345 (7.23); 1H-NMR(DMSO-d6, 6% w/v), δ 1.18 m (CH3), 2.05 m (CH2CH2CO), 2.43 t (CH2CO), 4.08 m (CH2O), 4.32 m (CH2N, CHN), 6.31 s, 7.51 s (NH2), 6.67 d, 7.69 d (C6H4), 6.71 s (CH2NH), 8.25 d (CONH), 8.41 d (5 --CH, J=2.0 Hz), 8.66 d (7-CH, J=2.0 Hz).

후처리

  1. filtrationThe mixture was filtered
  2. washthe catalyst was washed with 70% acetic acid (25 ml)
  3. washThe combined filtrate and wash
  4. customwas evaporated to dryness under high vacuum
  5. filtrationa solution of the residue in ethanol was filtered into 2 N Na2CO3 (60 ml)
  6. customto give a homogeneous powder which
  7. customwas collected
  8. washwashed with water
  9. customdried
  10. filtrationwas filtered hot
  11. customevaporated to dryness in vacuo
  12. customThe residue was triturated with CHCl3 (85 ml)
  13. filtrationcollected by filtration
  14. washthe solid was washed with additional CHCl3 (40 ml)
  15. additionA suspension of the solid
  16. stirringwas stirred for 20 minutes
  17. filtrationThe product was collected by filtration
  18. dry with materialdried in vacuo (P2O5)
  19. wait1H-NMR(DMSO-d6, 6% w/v), δ 1.18 m (CH3), 2.05 m (CH2CH2CO), 2.43 t (CH2CO), 4.08 m (CH2O), 4.32 m (CH2N, CHN), 6.31 s, 7.51 s
  20. custom(NH2), 6.67 d, 7.69 d (C6H4), 6.71 s (CH2NH), 8.25 d (CONH), 8.41 d (5 --CH, J=2.0 Hz), 8.66 d (7-CH, J=2.0 Hz)

출처 및 근거

ORD 기록
ord-e909ffbdc267401f81365317aa491d14
출처 데이터셋
uspto-grants-1984_02
특허 번호
US04431805

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