Dimethylformamide → 2,4-Dioxo-3-[(2-pheyl-pyrimidine-5-carbonyl)-amino]-1,2,3,4-tetrahydro-pyrimidin-5-yl-propionic acid methyl ester

HRID 2381975Notes

Reaction equation

HRID 2381975 reaction equation
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.C1CCC(N=C=NC2CCCCC2)CC1.COC(=O)[CH2:44][CH2:45][C:46]1[C:47](=[O:54])[N:48]([NH2:53])[C:49](=[O:52])[NH:50][CH:51]=1.[CH2:56]([OH:63])C(N)(CO)CO.CN([CH:67]=[O:68])C>>[CH3:67][O:68][C:56](=[O:63])[CH:45]([C:46]1[C:47](=[O:54])[N:48]([NH:53][C:13]([C:10]2[CH:11]=[N:12][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8][CH:9]=2)=[O:15])[C:49](=[O:52])[NH:50][CH:51]=1)[CH3:44]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 6503Tris(hydroxymethyl)aminomethane2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7473892-Phenylpyrimidine-5-carboxylic acidHCID 866393703-Amino-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-propionic acid methyl ester

Product 1

HCID 1317299362,4-Dioxo-3-[(2-pheyl-pyrimidine-5-carbonyl)-amino]-1,2,3,4-tetrahydro-pyrimidin-5-yl-propionic acid methyl esterYield 25%

Procedure

A mixture of 2-phenyl-pyrimidine-5-carboxylic acid (1.17 mmol), 1-hydroxybenzotriazole (1.99 mmol), and PS-DCC (1.21 mmol/g, 2.34 mmol in DMF (8 mL) is shaken at rt for 60 min. 3-{3-Amino-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-propionic acid methyl ester (1.17 mmol) is added and the mixture is shaken at rt for 2-4 days. Polymer supported-trisamine (PS-trisamine) (4.08 mmol/g, 3.51 mmol) is added and the mixture is continually shaken at rt for 18 hours. The solid is filtered and washed with MeOH. The filtrate is concentrated. The residue is purified by silica gel chromatography eluting with 10-60% EtOAc in hexanes to afford 3-{2,4-dioxo-3-[(2-pheyl-pyrimidine-5-carbonyl)-amino]-1,2,3,4-tetrahydro-pyrimidin-5-yl-propionic acid methyl ester (115 mg, 25%) as a solid. MS: 397 (M+H) 397; 1H NMR (300 MHz, CDCl3): δ 2.57-2.76 (m, 2H), 2.80-3.00 (m, 2H), 3.64 (s, 3H), 5.30 (br. N—H), 7.37-7.55 (m, 3H), 8.35 (d, 2H), 9.26 (s, 2H).

Workup

  1. stirringthe mixture is shaken at rt for 2-4 days
  2. additionis added
  3. stirringthe mixture is continually shaken at rt for 18 hours
  4. filtrationThe solid is filtered
  5. washwashed with MeOH
  6. concentrationThe filtrate is concentrated
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 10-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-86daf5c2a72348be89384a19c904e6fd
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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