Sodium Carbonate → (S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-methylurea

HRID 1626559Notes

Reaction equation

HRID 1626559 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]2[CH3:21])[C:5]2[CH2:10][N:9]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[CH2:8][C:6]=2[N:7]=1.[CH3:22][NH:23][C:24]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1)=[O:25].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O>[CH:12]1([CH2:11][N:9]2[CH2:10][C:5]3[C:4]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]4[CH3:21])=[N:3][C:2]([C:30]4[CH:29]=[CH:28][C:27]([NH:26][C:24]([NH:23][CH3:22])=[O:25])=[CH:32][CH:31]=4)=[N:7][C:6]=3[CH2:8]2)[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 177502733-Methyl-1-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 86663153(S)-4-(2-chloro-6-(cyclopropylmethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 46912495(S)-1-(4-(6-(cyclopropylmethyl)-4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)-3-methylureaYield 51.5%

Reagents, catalysts & solvents 1

HCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (S)-4-(2-chloro-6-(cyclopropylmethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-3-methylmorpholine (intermediate 8) (50 mg, 0.16 mmol) and 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (407 mg, 0.39 mmol) in DME/EtOH/H2O (7:3:2) (5 mL) was added Pd(PPh3)2(Cl)2 (7 mg, 0.008 mmol) and Na2CO3 (26 mg, 0.24 mmol). The reaction mixture was then heated by microwave at 130° C. for 30 minutes. The crude reaction mixture was then partitioned between water and EtOAc, the organic layer recovered, dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by prep. LCMS (low pH). The solvent was removed in vacuo. The residue was then re-purified by Flash SCX2 column chromatography, affording the title compound as a white solid (34.8 mg, 51% yield).

Workup

  1. customThe crude reaction mixture
  2. customwas then partitioned between water and EtOAc
  3. customthe organic layer recovered
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by prep
  8. customThe solvent was removed in vacuo
  9. customThe residue was then re-purified by Flash SCX2 column chromatography

Sources & evidence

ORD record
ord-539a05cab0bd44d5948cf6011b0e7d27
Source dataset
uspto-grants-2014_07
Patent number
US08785457B2

Reaction notes

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