HCID 178471557, compound → HCID 178471559, compound

HRID 704872Notes

Reaction equation

HRID 704872 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, 13 H), 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. Anal. Calcd. for C30H37N5O7 : C, 61.73; H, 7.08; N, 12.00. Found: C, 44.56; H, 3.85; N, 17.30; Br, 24.38.

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-c571f3b3d0c848bcae25d6db2734b69e
Source dataset
uspto-grants-1991_01
Patent number
US04988813

Reaction notes

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