Triethylamine → (R)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea

HRID 1626712Notes

Reaction equation

HRID 1626712 reaction equation
Cl.[CH:2]1([NH:5][C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]=[C:17]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][C@H:25]4[CH3:30])[C:18]4[CH2:23][NH:22][CH2:21][C:19]=4[N:20]=3)=[C:11]([F:31])[CH:10]=2)=[O:7])[CH2:4][CH2:3]1.CCN(CC)CC.[CH:39]1([C:42](Cl)=[O:43])[CH2:41][CH2:40]1>CN(C=O)C>[CH:39]1([C:42]([N:22]2[CH2:23][C:18]3[C:17]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][C@H:25]4[CH3:30])=[N:16][C:15]([C:12]4[CH:13]=[CH:14][C:9]([NH:8][C:6]([NH:5][CH:2]5[CH2:3][CH2:4]5)=[O:7])=[CH:10][C:11]=4[F:31])=[N:20][C:19]=3[CH2:21]2)=[O:43])[CH2:41][CH2:40]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 66687170(R)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea hydrochloride2×

Product 1

HCID 66679064(R)-1-(4-(6-(cyclopropanecarbonyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-cyclopropylurea

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

To a stirring solution of (R)-1-cyclopropyl-3-(3-fluoro-4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea hydrochloride (intermediate 33) (112 mg, 0.25 mmol) in DMF (2 ml), was added Et3N (70 μL, 0.5 mmol). Reaction mixture was stirred at room temperature (20° C.) for 2 minutes followed by the addition of cyclopropanecarbonyl chloride (23 μL, 0.25 mmol) followed by stirring at room temperature for two hours. The reaction mixture was concentrated in vacuo before partitioning between water (10 ml) and DCM (10 ml). The organic layer was recovered, passed through a hydrophobic frit and the solvent removed in vacuo. Residue was then purified by prep. HPLC at high pH to afford the title compound as an off white solid (25 mg, 0.052 mmol, 21%).

Workup

  1. customReaction mixture
  2. stirringby stirring at room temperature for two hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. custombefore partitioning between water (10 ml) and DCM (10 ml)
  5. customThe organic layer was recovered
  6. customthe solvent removed in vacuo
  7. customResidue was then purified by prep

Sources & evidence

ORD record
ord-6b0bd277a5754e8dbf6639347f9d25f9
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

Loading…