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 1887197노트

반응식

HRID 1887197 반응식
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]

참가 물질

6

반응물 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

생성물 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 acid수율 42.3%

시약·촉매·용매 2

HCID 962Water용매2회HCID 312751,4-Dioxane용매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-209d76e260c648f5a9eb517d4ffb59d6
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501749B2

반응 노트

불러오는 중…