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

HRID 1438189Notes

Reaction equation

HRID 1438189 reaction equation
[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]

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 40A (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 tolouene). 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. 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).

Workup

  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

Sources & evidence

ORD record
ord-0b3afa86dad749069fa7d096ef177c53
Source dataset
uspto-grants-2009_11
Patent number
US07622585B2

Reaction notes

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