Methanol → HCID 135990644, compound

HRID 1638598Notes

Reaction equation

HRID 1638598 reaction equation
[C:1]([NH:4][C:5]1[NH:6][C:7](=[O:19])[C:8]2[CH2:14][CH2:13][CH:12](O)[N:11]([C:16](=[O:18])[CH3:17])[C:9]=2[N:10]=1)(=[O:3])[CH3:2].[NH2:20][C:21]1[CH:40]=[CH:39][C:24]([C:25]([NH:27][C@H:28]([C:35]([O:37][CH3:38])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])=[CH:23][CH:22]=1.CO.C([BH3-])#N.[Na+]>C(Cl)(Cl)Cl.CCO.C1C=CC=CC=1.C(O)(=O)C>[C:1]([NH:4][C:5]1[NH:6][C:7](=[O:19])[C:8]([CH2:14][CH2:13][CH2:12][NH:20][C:21]2[CH:22]=[CH:23][C:24]([C:25]([NH:27][C@H:28]([C:35]([O:37][CH3:38])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])=[CH:39][CH:40]=2)=[C:9]([NH:11][C:16](=[O:18])[CH3:17])[N:10]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 887MethanolHCID 5003444Sodium cyanoborohydride2×HCID 12469743Dimethyl N-(4-aminobenzoyl)-L-glutamateHCID 136082964HCID 136082964, compound

Product 1

HCID 135990644HCID 135990644, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolvent2×HCID 241BenzeneSolventHCID 702EthanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of 2.30 g (7.6 mmol) of 2-acetamido-8-acetyl-5,6,7,8-tetra hydro-7-hydroxypyrido[2,3-d]pyrimidin-4(3H)-one, 2.40 g (8.15 mmol) of dimethyl N-(4-aminobenzoyl)-L-glutamate, 5 g of 3A molecular sieves, 150 ml of methanol, and 4 ml of acetic acid was stirred with protection from moisture for 3 hours when "imine" formation was complete. Sodium cyanoborohydride (0.38 g) and 8 ml of acetic acid was added to the reaction. After 15 hours a trace of intermediate "imine" was detected by TLC and an additional 50 mg of sodium cyanoborohydride was added. After 1 hour the reaction was diluted with 500 ml of chloroform and filtered through a Celite pad to remove the insolubles. The chloroform solution was washed with four 50 ml portions of 5% aqueous sodium bicarbonate, two 50 ml portions of water, one 50 ml portion of brine, dried over magnesium sulphate and spin evaporated in vacuo. The resultant foam was triturated with 50 ml of ethyl acetate to give white crystals; yield, 2.75 g (65%), mp 144°-150°. Recrystallization from ethanol gave chromatographically pure material; yield, 1.70 g (40%), mp 135°-142°. An analytically pure sample was obtained from a previous run with mp 140°-143°; TLC: (C6H6 : EtOH/10:1); NMR (DMSO-d6)δ11.69 (br s, 2H, 2AcNH) 9.68 (br s, 1H, ring NH), 8.24 (br d, 1H, ArCONH), 7.65 (d, 2H, ArH), 6.53 (d, 2H, ArH), 6.17 (br t, 1H, CH2NH), 4.39 (m, 1H, CHCO2CH3), 3.63 (s, 3H, CO2CH3), 3.58 (s, 3H, CO2CH3), 3.01 (m, 2H, CH2NHAr), 2.43 (m, 2H, CH2CO2CH3), 2.1 (4H, pyrimidine --CH2 and CHCH2, masked by AcNH peaks), 2.14 (s, 3H, Ac), 2.01 (s, 3H, Ac), 1.72 (m, 2H, CH2CH2CH2).

Workup

  1. filtrationfiltered through a Celite pad
  2. customto remove the insolubles
  3. washThe chloroform solution was washed with four 50 ml portions of 5% aqueous sodium bicarbonate, two 50 ml portions of water, one 50 ml portion of brine
  4. dry with materialdried over magnesium sulphate
  5. customspin evaporated in vacuo
  6. customThe resultant foam was triturated with 50 ml of ethyl acetate
  7. customto give white crystals
  8. customyield
  9. customRecrystallization from ethanol
  10. customgave chromatographically pure material
  11. customyield
  12. customAn analytically pure sample was obtained from a previous run with mp 140°-143°

Sources & evidence

ORD record
ord-4fbbd918205a41d996d7c10ab2ea8b0c
Source dataset
uspto-grants-1989_11
Patent number
US04880812

Reaction notes

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