HCID 178471557, compound → HCID 178471559, compound

HRID 1199820Notes

Reaction equation

HRID 1199820 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:42])[C:11]2[CH:17]=[C:16]([C:18]#[C:19][C:20]3[CH:41]=[CH:40][C:23]([C:24]([NH:26][C@H:27]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:25])=[CH:22][CH:21]=3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]>[Pd].FC(F)(F)C(O)=O.C(Cl)Cl>[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:42])[C:11]2[CH2:17][CH:16]([CH2:18][CH2:19][C:20]3[CH:41]=[CH:40][C:23]([C:24]([NH:26][C@H:27]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:25])=[CH:22][CH:21]=3)[CH2:15][NH:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5]

Participants

5

Reactant 1

HCID 178471557HCID 178471557, compound

Product 1

HCID 178471559HCID 178471559, compoundYield 100.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of 0.59 g of diethyl N-[4-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-ylethynyl)benzoyl]-L-glutamate and 1.5 g of 5% palladium on charcoal in 30 ml of trifluoroacetic acid is hydrogenated at 53 psi at room temperature for 24.5 hours. The reaction mixture is diluted with methylene chloride and filtered through Celite. The solvent is removed under reduced pressure. The residue is redissolved in methylene chloride and extracted with a saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue chromatographed on silica gel using a 4% methanol:methylene chloride mixture as the eluent. Evaporation of the eluate yields 0.60 g (100%) of diethyl N-(4-[2-(2-pivaloylamino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl)-L-glutamate as a white solid: m.p. >250° C.; NMR (CDCl3, 300 MHz) delta 1.22 (t, 3H, J=7.20 Hz), 1.29 (s, 9H), 1.30 (t, 3H, J=7.20 Hz), 1.61-3.35 (m, 13H), 4.11 (q, 2H, J=7.20 Hz), 4.23 (q, 2H, J=7.20 Hz), 4.77-4.84 (m, 1H), 5.15 (brs, 1H), 7.17 (d, 1H, J=7.50 Hz), 7.23 (d, 2H, J=8.10 Hz), 8.56 (brs, 1H); IR (KBr) 3400, 3280, 2980, 1735, 1630, 1570, 1460, 1390, 1350, 1310, 1200, 1155, 1025, 930, and 800 cm-1.

Workup

  1. filtrationfiltered through Celite
  2. customThe solvent is removed under reduced pressure
  3. dissolutionThe residue is redissolved in methylene chloride
  4. extractionextracted with a saturated sodium bicarbonate solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent is removed under reduced pressure
  7. customthe residue chromatographed on silica gel using a 4% methanol
  8. customEvaporation of the

Sources & evidence

ORD record
ord-5b52097cfb52416d99684d5a375795ec
Source dataset
uspto-grants-1990_02
Patent number
US04902796

Reaction notes

Loading…