Phosgene → (R)-3-(4-(isopropylsulfonyl)-3-(pyrrolidin-2-yl)phenyl)-1,1-dimethylurea hydrochloride

HRID 1515521ノート

反応式

HRID 1515521 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:20]([CH:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[C:6]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2C(OC(C)(C)C)=O)[CH:7]=1.[C:26](=[O:29])(O)[O-].[Na+].C(Cl)([Cl:33])=O.[CH2:35]([N:37](CC)[CH2:38]C)C.Cl.CNC>ClCCl>[ClH:33].[CH:23]([S:20]([C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:26](=[O:29])[N:37]([CH3:38])[CH3:35])=[CH:7][C:6]=1[C@H:8]1[CH2:12][CH2:11][CH2:10][NH:9]1)(=[O:21])=[O:22])([CH3:24])[CH3:25]

参加物

7

反応物 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 516892Sodium BicarbonateHCID 57942759(R)-tert-butyl 2-(5-amino-2-(isopropylsulfonyl)phenyl)pyrrolidine-1-carboxylate

生成物 1

HCID 68439178(R)-3-(4-(isopropylsulfonyl)-3-(pyrrolidin-2-yl)phenyl)-1,1-dimethylurea hydrochloride

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To 1F (0.25 g, 0.68 mmol) in dichloromethane (5 mL) at 0° C. was added sodium bicarbonate (0.57 g, 6.8 mmol), then phosgene (0.71 mL, 1.36 mmol, 20% in toluene). The reaction was stirred at 0° C. for 30 min. The crude mixture was filtered and washed with dichloromethane. To the filtrate was added triethylamine (0.27 mL, 2.04 mmol), then dimethylamine hydrochloride (0.083 g, 1.02 mmol) and the reaction was stirred for 2 h at rt. The solution was washed with water and brine and dried over sodium sulfate. The solvent was removed and the residue was redissolved in ethyl acetate (2 mL). HCl (4 mL, 4M in dioxane) was added and the reaction was stirred at rt for 4 h. The solvent was removed and dried under high vacuo to give 31A. 1H NMR (400 MHz, Methanol-d4) δ ppm 1.23 (d, J=6.59 Hz, 3H) 1.31-1.40 (m, 3H) 2.14-2.27 (m, 1H) 2.29-2.43 (m, 2H) 2.44-2.60 (m, 1H) 3.02-3.11 (m, 6H) 3.37-3.53 (m, 3H) 5.42 (t, J=7.69 Hz, 1H) 7.64 (dd, J=8.79, 1.76 Hz, 1H) 7.91 (d, J=8.79 Hz, 1H) 8.08 (d, J=2.20 Hz, 1H).

後処理

  1. filtrationThe crude mixture was filtered
  2. washwashed with dichloromethane
  3. washThe solution was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed
  6. dissolutionthe residue was redissolved in ethyl acetate (2 mL)
  7. additionHCl (4 mL, 4M in dioxane) was added
  8. stirringthe reaction was stirred at rt for 4 h
  9. customThe solvent was removed
  10. customdried under high vacuo

出典と根拠

ORDレコード
ord-4be72812c2574ce490c0298ae69e54e0
出典データセット
uspto-grants-2012_07
特許番号
US08222453B2

反応ノート

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