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

HRID 1626684Notes

Reaction equation

HRID 1626684 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:5]2[CH2:10][N:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH:22]1([NH:25][C:26]([NH:28][C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[C:31]([F:44])[CH:30]=2)=[O:27])[CH2:24][CH2:23]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:22]1([NH:25][C:26](=[O:27])[NH:28][C:29]2[CH:34]=[CH:33][C:32]([C:2]3[N:3]=[C:4]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[C:5]4[CH2:10][N:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][C:6]=4[N:7]=3)=[C:31]([F:44])[CH:30]=2)[CH2:23][CH2:24]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 86663171ethyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate2×

Product 1

HCID 66678972Ethyl 2-(4-(3-cyclopropylureido)-2-fluorophenyl)-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateYield 3.4%

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 ethyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 27) (156 mg, 0.498 mmol), 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (182 mg, 0.567 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (20 mg, 0.0249 mmol) and sodium carbonate (148 mg, 1.39 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 to give a solid which was then triturated in MeOH to yield the title compound (8 mg, 3%).

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. customto give a solid which
  8. customwas then triturated in MeOH

Sources & evidence

ORD record
ord-0d0b0920666946b092619e7691a97d4a
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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