Cesium carbonate → HCID 52935514, compound

HRID 1891120Notes

Reaction equation

HRID 1891120 reaction equation
Cl.Cl.[NH2:3][CH2:4][C@:5]1([OH:13])[CH2:11][N:10]2[CH2:12][C@@H:6]1[CH2:7][CH2:8][CH2:9]2.[N:14]([C:17]1[N:18]=[CH:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:15]=S.C(=O)([O-])[O-].[Cs+].[Cs+].C(N=C=NC(C)C)(C)C>CN(C=O)C>[CH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:26]=[C:17]([NH:14][C:15]2[O:13][C@:5]3([CH2:11][N:10]4[CH2:12][C@@H:6]3[CH2:7][CH2:8][CH2:9]4)[CH2:4][N:3]=2)[N:18]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 12734DiisopropylcarbodiimideHCID 574765653-IsothiocyanatoisoquinolineHCID 86658976HCID 86658976, compound

Product 1

HCID 52935514HCID 52935514, compoundYield 20.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To (5S*,6S*)-6-(aminomethyl)-1-azabicyclo[3.2.1]octan-6-ol dihydrochloride (84 mg, 0.54 mmol) in DMF (3 mL) was added 3-isothiocyanatoisoquinoline (100 mg, 0.54 mmol) and cesium carbonate (526 mg, 1.61 mmol). The reaction was heated to 80° C. for 2 hours and then treated with 1,3-diisopropylcarbodiimide (0.168 mL, 1.08 mmol). The reaction was maintained at 80° C. for 18 hours and then cooled to room temperature. The crude reaction was purified by silica gel chromatography, eluting with 5-40% (10% NH4OH/methanol) in chloroform. The desired product was collected and concentrated to give (5S*,5′R*)—N-(isoquinolin-3-yl)-4′H-1-azaspiro[bicyclo[3.2.1]octane-6,5′-oxazol]-2′-amine as a yellow solid (34 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.15 (br. s., 1H) 8.96 (s, 1H) 7.86 (d, J=8.03 Hz, 1H) 7.70 (d, J=8.28 Hz, 1H) 7.55 (t, J=7.28 Hz, 1H) 7.31-7.42 (m, 2H) 4.10 (d, J=9.03 Hz, 1H) 3.96 (d, J=9.03 Hz, 1H) 3.60 (d, J=14.05 Hz, 1H) 3.31 (d, J=11.80 Hz, 1H) 3.09 (dd, J=14.05, 2.01 Hz, 1H) 2.81-3.01 (m, 3H) 2.30 (d, J=3.01 Hz, 1H) 1.74-1.91 (m, 2H) 1.42-1.58 (m, 2H). MS: (LC/MS) RT=0.797 mins [M+H]=309.01.

Workup

  1. temperatureThe reaction was maintained at 80° C. for 18 hours
  2. temperaturecooled to room temperature
  3. customThe crude reaction
  4. customwas purified by silica gel chromatography
  5. washeluting with 5-40% (10% NH4OH/methanol) in chloroform
  6. customThe desired product was collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cac661cff5e74a2e9644c35532d12d68
Source dataset
uspto-grants-2013_08
Patent number
US08507516B2

Reaction notes

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