Dichloromethane → Methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626698Notes

Reaction equation

HRID 1626698 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[C:30]([F:43])[CH:29]=2)=[O:26])[CH2:23][CH2:22]1.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>[CH:21]1([NH:24][C:25](=[O:26])[NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:2]3[N:3]=[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]4[CH2:10][N:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:8][C:6]=4[N:7]=3)=[C:30]([F:43])[CH:29]=2)[CH2:22][CH2:23]1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666792291-Cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea2×HCID 86663169methyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2×

Product 1

HCID 66678810Methyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateYield 22%

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 methyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 25) (10 mg, 0.335 mol), 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (122 mg, 0.382 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (14 mg, 0.0168 mmol) and sodium carbonate (107 mg, 1.01 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 redissolved in a mix of MeOH/DCM. It was loaded onto an SCX cartridge and washed with two column volumes of MeOH/DCM before being eluted with 2M NH3 in MeOH and concentrated in vacuo. The sample was then purified via preparative HPLC at low pH to yield the title compound (33 mg, 22%).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe residue redissolved in
  3. additiona mix of MeOH/DCM
  4. washwashed with two column volumes of MeOH/DCM
  5. washbefore being eluted with 2M NH3 in MeOH
  6. concentrationconcentrated in vacuo
  7. customThe sample was then purified via preparative HPLC at low pH

Sources & evidence

ORD record
ord-d1ed7572b7554c23a3ab8595bb820789
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

Loading…