HCID 178418361, compound → HCID 178471580, compound

HRID 2350906Notes

Reaction equation

HRID 2350906 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:45])[C:11]2[CH:17]=[C:16]([CH2:18][N:19]([CH2:22][C:23]3[CH:44]=[CH:43][C:26]([C:27]([NH:29][C@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:28])=[CH:25][CH:24]=3)[CH:20]=[O:21])[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[H][H]>C(O)(=O)C.[Pt]=O>[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:45])[C:11]2[CH2:17][CH:16]([CH2:18][N:19]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([C:27]([NH:29][C@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:28])=[CH:43][CH:44]=3)[CH:20]=[O:21])[CH2:15][NH:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5]

Participants

5

Reactant 2

HCID 178418361HCID 178418361, compoundHCID 178471579HCID 178471579, compound

Product 1

HCID 178471580HCID 178471580, compoundYield 750.9%

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 1.09 g. (0.17 mmol) of diethyl N-[N-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-ylmethyl)-N-formyl-4-aminomethylbenzoyl]-glutamate in 50 mL of glacial acetic acid was added 164 mg of platinum oxide. The suspension was shaken in a Parr hydrogenation apparatus under an atmosphere (50 psi) of hydrogen at 25° C. for 3 hours. The reaction mixture was filtered through Celite and the filtrate evaporated under reduced pressure. The residue was dissolved in 100 mL of methylene chloride and extracted twice with a saturated solution of sodium bicarbonate. The aqueous layers were back extracted with 75 mL of methylene chloride and the organic layers combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated under reduced pressure and the residue chromatographed, eluting with 5% methanol in methylene chloride to give 0.8 g of diethyl N-[N-(2-pivaloylamino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-ylmethyl)-N-formyl-4-aminomethylbenzoyl]-glutamate (73% yield). An analytical sample was recrystallized from acetonitrile; mp 149°-151° C.; 1H NMR (Me2SO d6) delta 1.11-1.16 (m, 6H), 1.18 (s, 9H), 1.83-2.15 (m, 4H), 2.30.varies.2.47 (m, 3H), 2.79-3.20 (m, 4H), 3.98-4.11 (m, 4H), 4.36-4.43 (m, 1H), 4.53-4.54 (m, 2H), 6.40-6.51 (m, 1H), 7.33-7.36 (m, 2H, AA'BB'), 7.80-7.85 (m, 2H, AA'BB'), 8.11 and 8.38 (s, 1H), 8.67-8.73 (m, 1 H). Anal. Calcd for C31H42N6O8 : C, 59.41; H, 6.75; N, 13.41. Found: C, 59.14; H, 6.73; N, 13.64.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. customthe filtrate evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in 100 mL of methylene chloride
  4. extractionextracted twice with a saturated solution of sodium bicarbonate
  5. extractionThe aqueous layers were back extracted with 75 mL of methylene chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated under reduced pressure
  9. customthe residue chromatographed
  10. washeluting with 5% methanol in methylene chloride

Sources & evidence

ORD record
ord-55c966b1204444f192a4cd0b6ca5204d
Source dataset
uspto-grants-1989_10
Patent number
US04871746

Reaction notes

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