Triethylamine → (R)-ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626703Notes

Reaction equation

HRID 1626703 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.C(N(CC)CC)C.Cl[C:40]([O:42][CH2:43][CH3:44])=[O:41]>CN(C=O)C>[CH:2]1([NH:5][C:6](=[O:7])[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][N:22]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:21][C:19]=4[N:20]=3)=[C:11]([F:31])[CH:10]=2)[CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 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 66679248(R)-ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 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) (121 mg, 0.270 mmol) and triethylamine (75 μL, 0.534 mmol) in anhydrous DMF (2 ml) was stirred at RT for 40 minutes. After this time, ethyl chloroformate (30 μl, 0.322 mmol) was added and stirring was continued at RT overnight. The reaction was partitioned between H2O and EtOAc and the aqueous phase was extracted into EtOAc. The organic extracts were combined, dried over magnesium sulphate and concentrated in vacuo. The sample was then purified via preparative HPLC at low pH to yield the title compound (35 mg, 27%).

Workup

  1. customThe reaction was partitioned between H2O and EtOAc
  2. extractionthe aqueous phase was extracted into EtOAc
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe sample was then purified via preparative HPLC at low pH

Sources & evidence

ORD record
ord-e167043d650f45a7aaf42d0cbdc578ed
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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