Acetic Acid → (R)-3-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid

HRID 1887197Notes

Reaction equation

HRID 1887197 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][C@H:5]([N:8]1[C:13](=[O:14])[C:12]2[N:15]=[CH:16][CH:17]=[CH:18][C:11]=2[N:10]([CH2:19][C:20]2[C:28]3[C:23](=[CH:24][C:25]([CH3:30])=[CH:26][C:27]=3[CH3:29])[N:22]([CH3:31])[CH:21]=2)[C:9]1=[O:32])[CH2:6][CH3:7].O.[OH-].[Li+].C(O)(=O)C>O.O1CCOCC1>[O:32]=[C:9]1[N:10]([CH2:19][C:20]2[C:28]3[C:23](=[CH:24][C:25]([CH3:30])=[CH:26][C:27]=3[CH3:29])[N:22]([CH3:31])[CH:21]=2)[C:11]2[CH:18]=[CH:17][CH:16]=[N:15][C:12]=2[C:13](=[O:14])[N:8]1[C@H:5]([CH2:6][CH3:7])[CH2:4][C:3]([OH:33])=[O:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 168937Lithium hydroxide, monohydrateHCID 67501927(R)-3-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid methyl ester

Product 1

HCID 46853762(R)-3-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acidYield 42.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A solution of 1.0 g of (R)-3-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid methyl ester and 187 mg of lithium hydroxide monohydrate in 20 mL water and 20 mL of 1,4-dioxane is stirred at room temperature for 3 h. The resulting mixture is neutralized with 0.26 mL of acetic acid and the resulting mixture is diluted with water. The product is extracted with ethyl acetate. The organic layer is washed with water and brine, dried (sodium sulfate), filtered and concentrated. The residue is purified by flash chromatography on silica gel. The combined fractions are concentrated and the residue is triturated with ether to give 410 mg (42%) of (R)-3-[2,4-dioxo-1-(1,4,6-trimethyl-1H-indol-3-ylmethyl)-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl]-pentanoic acid; LCMS (ESMS): m/z 435 (M+H+).

Workup

  1. extractionThe product is extracted with ethyl acetate
  2. washThe organic layer is washed with water and brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by flash chromatography on silica gel
  7. concentrationThe combined fractions are concentrated
  8. customthe residue is triturated with ether

Sources & evidence

ORD record
ord-209d76e260c648f5a9eb517d4ffb59d6
Source dataset
uspto-grants-2013_08
Patent number
US08501749B2

Reaction notes

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