Cesium carbonate → HCID 57991944, compound

HRID 2075350Notes

Reaction equation

HRID 2075350 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][C:17](=O)OC(C)(C)C)=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:30][C:31]([F:49])([F:48])[C:32]1[CH:37]=[CH:36][C:35]([C@H:38]2[C@@H:45]3[N:41](S(=O)(=O)OC3)[CH2:40][CH2:39]2)=[CH:34][CH:33]=1>CN(C=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][CH2:17][C@@H:45]4[C@H:38]([C:35]5[CH:36]=[CH:37][C:32]([C:31]([F:30])([F:48])[F:49])=[CH:33][CH:34]=5)[CH2:39][CH2:40][NH:41]4)=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 57991860HCID 57991860, compoundHCID 57991904HCID 57991904, compound

Product 1

HCID 57991944HCID 57991944, compoundYield 10.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
120 °C

Procedure

To a stirred mixture of tert-butyl 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylcarbamate (99 mg, 0.30 mmol) and cesium carbonate (154 mg, 0.47 mmol) in DMF (1.0 mL) was added slowly a solution of (3aS,4S)-4-(4-(trifluoromethyl)phenyl)tetrahydro-3H-pyrrolo[1,2-c][1,2,3]oxathiazole 1,1-dioxide (58 mg, 0.19 mmol) in DMF (1.0 mL) at 50° C. The mixture was stirred for 1 hour and then concentrated. The residue was dissolved in EtOH and acidified with 5 N HCl (˜pH 2). The mixture was heated at 120° C. for 20 minutes under microwave irradiation. The mixture was concentrated, and the residue was taken up in DCM (2 mL) and water (2 mL). The aqueous layer was made basic with 5 N NaOH and extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography (ISCO Combiflash system, eluting with a gradient of DCM to 10% MeOH in DCM) to provide 5-(isoquinolin-6-yl)-N-(((2S,3S)-3-(4-(trifluoromethyl)phenyl)pyrrolidin-2-yl)methyl)-1,3,4-thiadiazol-2-amine as a pale yellow solid (8.8 mg, 10%). LCMS (M+H) 456.1 calc. for C23H21F3N5S 456.1. 1H NMR (400 MHz, CDCl3): δ ppm 2.14-2.29 (m, 1H), 2.48-2.54 (m, 2H), 3.72-3.81 (m, 1H), 3.82-3.92 (m, 1H), 4.04-4.23 (m, 1H), 4.54-4.67 (m, 1H), 7.48 (d, J=7.53 Hz, 2H), 7.70 (d, J=8.03 Hz, 2H), 7.78 (d, J=5.02 Hz, 2H), 7.86-8.02 (m, 1H), 8.30 (d, J=3.01 Hz, 1H), 8.42-8.54 (m, 2H), 9.24 (s, 1H). 2H obscured.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in EtOH
  3. concentrationThe mixture was concentrated
  4. extractionextracted with EtOAc (3×5 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (ISCO Combiflash system
  9. washeluting with a gradient of DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-63578b646a3b42acbc2f80756b2d9a1c
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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