Dimethylformamide → 2-(2,6-Dimethylpyrimidin-4-yl)-5-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}octahydropyrrolo[3,4-c]pyrrole

HRID 244022Notes

Reaction equation

HRID 244022 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:23][CH:22]3[CH:18]([CH2:19][NH:20][CH2:21]3)[CH2:17]2)=[O:15])=[CH:4][CH:3]=1.CN(C=O)C.Cl[C:30]1[CH:35]=[C:34]([CH3:36])[N:33]=[C:32]([CH3:37])[N:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(OCC)(=O)C>[CH3:37][C:32]1[N:31]=[C:30]([N:20]2[CH2:19][CH:18]3[CH:22]([CH2:23][N:16]([C:14]([C:9]4[N:10]=[C:11]([CH3:13])[S:12][C:8]=4[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[O:15])[CH2:17]3)[CH2:21]2)[CH:35]=[C:34]([CH3:36])[N:33]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 31541994-Chloro-2,6-dimethylpyrimidineHCID 67116377(5-(4-Fluorophenyl)-2-methylthiazol-4-yl)(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)methanone

Product 1

HCID 671171872-(2,6-Dimethylpyrimidin-4-yl)-5-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}octahydropyrrolo[3,4-c]pyrroleYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of Intermediate 48 (15.8 mg, 0.048 mmol) was added DMF (0.4 mL), 4-chloro-2,6-dimethylpyrimidine (8.2 mg, 0.057 mmol) and cesium carbonate (38.8 mg, 0.119 mmol). The mixture was heated to 100° C. for 18 hours, diluted with water and extracte with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by reverse phase HPLC to give the title compound (12.9 mg, 62%). MS (ESI): mass calculated for C23H24FN5OS, 437.5; m/z found [M+H]+438.2. 1H NMR (400 MHz, CDCl3): 7.51-7.41 (m, 2H), 7.06-6.95 (m, 2H), 6.29 (s, 1H), 3.892-3.76 (m, 2H), 3.73-3.51 (m, 3H), 3.44 (dd, J=11.6, 5.0 Hz, 1H), 3.32 (dd, J=11.6, 4.5 Hz, 1H), 3.10 (dd, J=11.3, 5.3 Hz, 1H), 3.02-2.80 (m, 2H), 2.70 (s, 3H), 2.31 (d, J=20.0 Hz, 6H).

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. concentrationconcentrated
  3. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5a24e0cbd7c34001ae3bdd1b5e8a926f
Source dataset
uspto-grants-2014_02
Patent number
US08653263B2

Reaction notes

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