Dichloromethane → (S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-ethylurea

HRID 1626685Notes

Reaction equation

HRID 1626685 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[C:5]2[CH2:10][N:9]([C:11](=[O:13])[CH3:12])[CH2:8][C:6]=2[N:7]=1.[CH2:21]([NH:23][C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[C:29]([F:42])[CH:28]=1)=[O:25])[CH3:22].ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.O.COCCOC>[C:11]([N:9]1[CH2:10][C:5]2[C:4]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]3[CH3:20])=[N:3][C:2]([C:30]3[CH:31]=[CH:32][C:27]([NH:26][C:24]([NH:23][CH2:21][CH3:22])=[O:25])=[CH:28][C:29]=3[F:42])=[N:7][C:6]=2[CH2:8]1)(=[O:13])[CH3:12]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666787871-Ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 86663168(S)-1-(2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone2×

Product 1

HCID 66678973(S)-1-(4-(6-acetyl-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)-3-fluorophenyl)-3-ethylureaYield 4.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (S)-1-(2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidin-6(7H)-yl)ethanone (intermediate 24) (99 mg, 0.334 mmol), 1-ethyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 28) (103 mg, 0.334 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (14 mg, 0.0167 mmol) and sodium carbonate (99 mg, 0.934 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 115° C. for 45 minutes. The reaction was concentrated in vacuo and the residue was re-dissolved in a mix of H2O and EtOAc. The aqueous phase was basified by the addition of aqueous NaOH and extracted into EtOAc. The organic extracts were combined and concentrated in vacuo. The sample was purified via preparative HPLC at low pH, and then at high pH, to yield the title compound (6 mg, 4%).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue was re-dissolved in
  3. additiona mix of H2O and EtOAc
  4. additionThe aqueous phase was basified by the addition of aqueous NaOH
  5. extractionextracted into EtOAc
  6. concentrationconcentrated in vacuo
  7. customThe sample was purified via preparative HPLC at low pH

Sources & evidence

ORD record
ord-6a0a8bbfe4494ad9969ba2bb4203559e
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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