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 1525082Notes

Reaction equation

HRID 1525082 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>[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

6

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 1

HCID 962WaterSolvent

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 extract 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. extractionextract with ethyl acetate
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e8b556ec7c954e488a6d60d6b05a0d67
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

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