2-Methyl-2-thiopseudourea → HCID 178473458、化合物

HRID 12257

反応式

HRID 12257 の反応式
CS[C:3](=[NH:5])[NH2:4].Cl[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH-].[Na+].N[C:15]1[C:20]([NH2:21])=[CH:19][C:18]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:17][C:16]=1[C:28](=[O:31])[CH2:29][CH3:30]>O.CCOC(C)=O.CC(O)=O>[CH2:10]([O:9][C:7](=[O:8])[NH:4][C:3]1[NH:5][C:15]2[C:16]([C:28](=[O:31])[CH2:29][CH3:30])=[CH:17][C:18]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)=[CH:19][C:20]=2[N:21]=1)[CH3:11]

参加物

8

反応物 4

HCID 51422-Methyl-2-thiopseudoureaHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 179849121-(2,3-Diamino-5-pyridin-3-yl-phenyl)-propan-1-one

生成物 1

HCID 178473458HCID 178473458、化合物

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a mixture of 2-methyl-2-thiopseudourea (109 mg, 0.39 mmol) and ethyl chloroformate (75 μL, 0.78 mmol) in water (2 mL) at 5° C. was added over 40 minutes a 6N aqueous NaOH solution until pH stabilized to 8. The pH was then adjusted to 5 with glacial AcOH. A suspension of 1-(2,3-diamino-5-pyridin-3-yl-phenyl)-propan-1-one (0.30 mmol) in water (5 mL) was subsequently added to the reaction mixture. The reaction was heated at 90° C. for 18 hours, cooled to ambient temperature, and diluted with water (10 mL) and EtOAc (20 mL). The phases were separated and the aqueous layer extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. The crude residue was taken up in DMSO, purified by preparative HPLC, and by flash column chromatography (SiO2; CH2Cl2:MeOH, 1:0 to 19:1). The residue was then converted to the bis-HCl salt to afford the title compound as an off white solid (5.0 mg): HPLC (10 to 90% CH3CN, 8 min.): Rt=3.90 minutes; 1H NMR (CD3OD, 500 MHz) δ 9.39 (d, 1H), 9.07 (d, 1H), 8.93 (d, 1H), 8.48 (d, 1H), 8.28 (d, 1H), 8.25 (dd, 1H), 4.46 (q, 2H), 3.35 (q, 2H), 1.43 (t, 3H), 1.29 (t, 3H); MS (ES+) m/z (M++1) 339.1.

後処理

  1. additionwas subsequently added to the reaction mixture
  2. temperaturecooled to ambient temperature
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted with EtOAc (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-7c5490cbc6894f5eace522a61c214842
出典データセット
uspto-grants-2010_06
特許番号
US07727992B2

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