1-(2-Fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea → (S)-ethyl 2-(4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

HRID 1626634Notes

Reaction equation

HRID 1626634 reaction equation
[CH2:1]([NH:3][C:4](=[O:36])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]3[CH3:35])[C:15]3C[CH2:20][N:19]([C:22]([O:24][C:25](C)(C)[CH3:26])=[O:23])[CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)[CH3:2].ClC1N=C(N2CCOC[C@@H]2C)C2CN(C(OCC)=O)CC=2N=1.[F:59]CCNC(NC1C=CC(B2OC(C)(C)C(C)(C)O2)=CC=1)=O>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]>[F:59][CH2:2][CH2:1][NH:3][C:4](=[O:36])[NH:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:13]=[C:14]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]3[CH3:35])[C:15]3[CH2:20][N:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][C:16]=3[N:17]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 446073531-(2-Fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 59239149HCID 59239149, compoundHCID 86663155HCID 86663155, compound2×

Product 1

HCID 86663162(S)-ethyl 2-(4-(3-(2-fluoroethyl)ureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylateYield 13%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

Method as described for intermediate 5 using (S)-ethyl 2-chloro-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 11) and 1-(2-fluoroethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea as starting materials and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) as catalyst. The mixture was filtered through a celite 545 pre-packed cartridge (2.5 g), washed with MeOH and solvent removed in vacuo. The residue was purified first by flash chromatography using a gradient of 0-20% MeOH/DCM as eluent, then prep HPLC (low pH) yielding the title compound (9.2 mg, 0.02 mmol, 13%).

Workup

  1. filtrationThe mixture was filtered through a celite 545 pre-packed cartridge (2.5 g)
  2. washwashed with MeOH and solvent
  3. customremoved in vacuo
  4. customThe residue was purified first by flash chromatography

Sources & evidence

ORD record
ord-68d687f3ee254d01a650cebea0dee3c5
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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