Cyclopropylamine → HCID 178522431, compound

HRID 2088376Notes

Reaction equation

HRID 2088376 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]3[C:18](=[CH:19][CH:20]=2)[N:17]=[C:16]2[N:11]3[C:12](=[O:24])[NH:13][C:14]3[C:15]2=[N:21][NH:22][CH:23]=3)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:25]1([NH2:28])[CH2:27][CH2:26]1>CN1C(=O)CCC1.O>[CH:25]1([NH:28][C:12]([NH:13][C:14]2[C:15]([C:16]3[NH:17][C:18]4[CH:19]=[CH:20][C:8]([CH2:7][N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)=[CH:9][C:10]=4[N:11]=3)=[N:21][NH:22][CH:23]=2)=[O:24])[CH2:27][CH2:26]1

Participants

5

Reactant 2

HCID 69828Cyclopropylamine2×HCID 178518660HCID 178518660, compound

Product 1

HCID 178522431HCID 178522431, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 7-morpholin-4-ylmethyl-2,4-dihydro-1,2,4,5a,10-pentaaza-cyclopenta[a]fluoren-5-one (10.7 g, 32.9 mmol) in NMP (65 mL) was added cyclopropylamine (6.9 mL, 99 mmol). The mixture was heated at 100° C. for 5 h. LC/MS analysis indicated ˜75% conversion to product, therefore a further portion of cyclopropylamine (2.3 mL, 33 mmol) was added, the mixture heated at 100° C. for 4 h and then cooled to ambient. The mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL). The organic portion was washed with sat. aq. NH4Cl (2×50 mL) and brine (50 mL) and then the aqueous portions re-extracted with EtOAc (3×100 mL). The combined organic portions were dried over MgSO4 and reduced in vacuo to give 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea as an orange glassy solid (9.10 g).

Workup

  1. temperaturethe mixture heated at 100° C. for 4 h
  2. temperaturecooled
  3. extractionextracted with EtOAc (100 mL)
  4. washThe organic portion was washed with sat. aq. NH4Cl (2×50 mL) and brine (50 mL)
  5. extractionthe aqueous portions re-extracted with EtOAc (3×100 mL)
  6. dry with materialThe combined organic portions were dried over MgSO4

Sources & evidence

ORD record
ord-a1d7e33392114d5895753548a9d26064
Source dataset
uspto-grants-2013_05
Patent number
US08435970B2

Reaction notes

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