Sodium Carbonate → (S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

HRID 1626544노트

반응식

HRID 1626544 반응식
Cl[C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]2[CH3:25])[C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=2[N:7]=1.[CH2:26]([NH:28][C:29](=[O:46])[NH:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1)[CH3:27].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O>[CH2:26]([NH:28][C:29](=[O:46])[NH:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[N:3]=[C:4]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[C:5]3[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=3[N:7]=2)=[CH:33][CH:32]=1)[CH3:27]

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 44119377N-Ethyl-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 59239275Pyrido[3,4-d]pyriMidine-7(6H)-carboxylic acid, 2-chloro-5,8-dihydro-4-[(3S)-3-Methyl-4-Morpholinyl]-, 1,1-diMethylethyl ester2회

생성물 1

HCID 59239149(S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate수율 59.4%

시약·촉매·용매 1

HCID 86587095Dimethoxyethane ethanol water용매

반응 조건

온도
120 °C

실험 절차

To a solution of (S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (intermediate 4) (576 mg, 1.56 mmol) and 4-(3-ethylureido)phenylboronic acid pinacol ester (498 mg, 1.72 mmol) in DME/EtOH/H2O (12/5/3) (15 mL) was added Pd(PPh3)2(Cl)2 (55 mg, 0.078 mmol) and Na2CO3 (496 mg, 4.68 mmol). The reaction mixture was then heated by microwave at 120° C. for 1 h. The crude reaction mixture was then partitioned between water and EtOAc, the phases separated and the organic layer washed with aqueous NaHCO3 and brine, dried over magnesium sulfate, filtered and the solvent removed in vacuo. The residue was purified by flash chromatography (20-50% EtOAc/Petroleum Ether 40-60) to yield a yellow solid (460 mg, 59%).

후처리

  1. customThe crude reaction mixture
  2. customwas then partitioned between water and EtOAc
  3. customthe phases separated
  4. washthe organic layer washed with aqueous NaHCO3 and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by flash chromatography (20-50% EtOAc/Petroleum Ether 40-60)

출처 및 근거

ORD 기록
ord-76deec4061e542ffb62dc757fa2245bd
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785457B2

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