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

HRID 1626538ノート

反応式

HRID 1626538 の反応式
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]

参加物

5

反応物 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 ester2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 86587095Dimethoxyethane ethanol water溶媒

反応条件

温度
120 °C

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-ec1cc577e03748039398aacea59450a3
出典データセット
uspto-grants-2014_07
特許番号
US08785457B2

反応ノート

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