Hydrochloric Acid → HCID 178525920、化合物

HRID 2188758

反応式

HRID 2188758 の反応式
[OH:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:18].[F:26][C:27]([F:37])([F:36])[C:28]1[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O>[OH:1][C:2]1[N:7]([CH2:32][C:31]2[CH:34]=[CH:35][C:28]([C:27]([F:37])([F:36])[F:26])=[CH:29][CH:30]=2)[C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 178472773HCID 178472773、化合物

生成物 1

HCID 178525920HCID 178525920、化合物収率 30.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of ethyl N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycinate (example 11a, 356 mg, 1.03 mmoles), 4-trifluoromethylbenzyl bromide (175 uL, 1.13 mmoles) and sodium carbonate (330 mg, 3.1 mmoles) in dimethylformamide (6.0 mL) was stirred under argon at 100° C. for 2.5 hours. The mixture was cooled, poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The ester was hydrolysed by stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours. The mixture was acidified and extracted with ethyl acetate. Purification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water gave the title compound (150 mg, 30%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.12 (s, 1 H), 10.12 (t, J=5.56 Hz, 1 H), 7.69 (d, J=8.08 Hz, 2 H), 7.53 (d, J=8.08 Hz, 2 H), 7.24-7.35 (m, 5 H), 5.11 (s, 2 H), 5.03 (s, 2 H), 4.14 (d, J=5.81 Hz, 2 H).

後処理

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate (×2)
  3. stirringby stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours
  4. extractionextracted with ethyl acetate
  5. customPurification
  6. customby preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water

出典と根拠

ORDレコード
ord-789a78a7ebd64b318d2a0e54014f99fa
出典データセット
uspto-grants-2012_12
特許番号
US08324208B2

関連ノート

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