Methylurea → HCID 86677206, compound

HRID 340987Notes

Reaction equation

HRID 340987 reaction equation
[CH3:1][NH:2][C:3]([NH2:5])=O.[C:6]([OH:9])(=[O:8])C.[C:10](O)(=O)C.I[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:21](OC)(C)([CH3:23])[CH3:22]>>[CH:1]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:10]=[C:3]([NH:5][C:6](=[O:8])[O:9][CH2:22][CH2:21][CH3:23])[N:2]=1

Participants

4

Reactant 3

HCID 11719MethylureaHCID 15413tert-Butyl methyl etherHCID 12217721Iodo benzene diacetate

Product 1

HCID 86677206HCID 86677206, compound

Conditions

Temperature
55 °C

Procedure

A 500 mL 3-neck RBF was equipped with magnetic stirrer, heating mantle, set-point controller, thermowell, thermocouple and nitrogen bubbler. The flask was charged with 3-(2-chloro-3-fluorobenzyl)-1-(S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-hydroxypropan-2-yl)-1-methylurea (15.7 g, 41.9 mmol), iodobenzene diacetate (27 g, 2.0 equiv.) and methyl tert-butyl ether (141 mL). The mixture was warmed to ˜55° C. and the amide (7.6 g, 1.05 equiv.) was added in small portions. The reaction was stirred for 1 h. The reaction was cooled to ambient temperature and quenched by addition of saturated aq. NaHCO3 (150 mL). The organic phase was extracted with ethyl acetate, and the combined organics were washed with water and brine. The organic phase was dried over MgSO4 and concentrated. Residual solvents were removed by azeotrope from DCM and hexanes (3×) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(R)-2,2-dimethyl-1,3-dioxolan-4-yl)propyl isoquinolin-3-ylcarbamate as a solid (25.3 g), which was used without further purification. LRMS (M+H+) m/z 545.1.

Workup

  1. customA 500 mL 3-neck RBF was equipped with magnetic stirrer
  2. temperatureheating mantle
  3. temperatureThe reaction was cooled to ambient temperature
  4. customquenched by addition of saturated aq. NaHCO3 (150 mL)
  5. extractionThe organic phase was extracted with ethyl acetate
  6. washthe combined organics were washed with water and brine
  7. dry with materialThe organic phase was dried over MgSO4
  8. concentrationconcentrated
  9. customResidual solvents were removed by azeotrope from DCM and hexanes (3×)

Sources & evidence

ORD record
ord-df88d5b1dde841b89a6a38626e864cf0
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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