1-(Chloromethoxy)-2-methoxyethane → 1-[3-(2-methoxy-ethoxymethyl)-4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1428860ノート

反応式

HRID 1428860 の反応式
CCN(C(C)C)C(C)C.[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[NH:29][C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]4[CH2:34][CH2:33][CH2:32][CH2:31][C:25]=4[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11].C(OC(C1C=NN(C2NC(=O)C3C4CCCCC=4C=CC=3N=2)C=1)=O)C.Cl[CH2:61][O:62][CH2:63][CH2:64][O:65][CH3:66]>C1COCC1.CCOC(C)=O>[CH2:10]([O:12][C:13]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[N:29]([CH2:61][O:62][CH2:63][CH2:64][O:65][CH3:66])[C:28](=[O:30])[C:27]3[C:22](=[CH:23][C:24]4[CH2:34][CH2:33][CH2:32][CH2:31][C:25]=4[CH:26]=3)[N:21]=2)[CH:19]=1)=[O:14])[CH3:11]

参加物

7

反応物 4

HCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 81531DiisopropylethylamineHCID 1363371811-(4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl esterHCID 1363371821-(1-oxo-1,2,7,8,9,10-hexahydro-benzo[f]quinazolin-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

生成物 1

HCID 684848471-[3-(2-methoxy-ethoxymethyl)-4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester収率 41%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

DIEA (0.76 mL, 4.4 mmol) was added to a 2:1 mixture of 1-(4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester and 1-(1-oxo-1,2,7,8,9,10-hexahydro-benzo[f]quinazolin-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.500 g, 1.478 mmol) in THF (7.4 mL), followed by 1-chloromethoxy-2-methoxy-ethane (0.186 mL, 1.63 mmol). The reaction mixture was stirred at room temperature for 18 h, diluted with EtOAc (40 mL), and washed with water (30 mL). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers were washed with brine (40 mL), dried (MgSO4), and concentrated. The residue was purified by FCC (5-60% EtOAc/hexanes) to yield 1-[3-(2-methoxy-ethoxymethyl)-4-oxo-3,4,6,7,8,9-hexahydro-benzo[g]quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.257 g, 41% yield) and the titled compound (69.0 mg, 11% yield).

後処理

  1. washwashed with water (30 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  3. washthe combined organic layers were washed with brine (40 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by FCC (5-60% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-0b8bd14f598a407f94acd25b064ebf3a
出典データセット
uspto-grants-2015_01
特許番号
US08937078B2

反応ノート

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