Hydrochloric Acid → N-(6-methoxybenzo[d]thiazol-2-yl)-4'H-1-azaspiro[bicyclo[3.2.1]octane-6,5'-oxazol]-2'-amine

HRID 1891118Notes

Reaction equation

HRID 1891118 reaction equation
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]2[N:7]=[C:8]([NH:10][C:11]([N:13]3[CH:17]=[CH:16]N=C3)=S)[S:9][C:5]=2[CH:4]=1.[CH:20](N=C=NC(C)C)([CH3:22])[CH3:21].C(Cl)(Cl)Cl.[OH2:33].Cl.[CH3:35][N:36]([CH:38]=O)[CH3:37]>O>[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]2[N:7]=[C:8]([NH:10][C:11]3[O:33][C:16]4([CH2:37][N:36]5[CH2:38][CH:21]4[CH2:20][CH2:22][CH2:35]5)[CH2:17][N:13]=3)[S:9][C:5]=2[CH:4]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 22418719Chloroform water2×HCID 58088280N-(6-Methoxybenzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamide

Product 1

HCID 75965534N-(6-methoxybenzo[d]thiazol-2-yl)-4'H-1-azaspiro[bicyclo[3.2.1]octane-6,5'-oxazol]-2'-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

((1R*,5S*,6S*)-(6-(aminomethyl)-6-hydroxy-1-ammoniobicyclo[3.2.1]octan-1-yl)trihydroborate (300 mg, 1.76 mmol) and N-(6-methoxybenzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamide (615 mg, 2.117 mmol) were combined in DMF (5 mL). The reaction was heated to 70° C. for 2 hours and then treated with N,N′-Diisopropylcarbodiimide (1.37 mL, 8.82 mmol). The reaction was then heated an additional 2 hours and cooled to room temperature. The reaction was poured into a chloroform/water mixture and the organic was collected and dried to a residue. The residue was taken up in acetone (6 ml) and treated with hydrochloric acid (3 mL, 3M, 9.00 mmol). The reaction was stirred at room temperature for 3 hours and then poured into a chloroform/water mixture. The organic was discarded and the water layer was neutralized to pH 7. The neutralized layer was extracted in chloroform and the chloroform was removed in vacco to give a crude mixture. This mixture was purified by PREP HPLC. The desired compound fractions were combined and diluted with saturated sodium bicarbonate. The solution was then extracted several times with chloroform. The chloroform layers were combined and concentrated to give N-(6-methoxybenzo[d]thiazol-2-yl)-4′H-1-azaspiro[bicyclo[3.2.1]octane-6,5′-oxazol]-2′-amine as a white powder (13.1.1 mg, 3%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.04-9.55 (m, 1H) 7.50 (d, J=8.78 Hz, 1H) 7.15 (d, J=2.51 Hz, 1H) 6.91 (dd, J=8.91, 2.64 Hz, 1H) 4.11 (d, J=9.79 Hz, 1H) 3.97-4.07 (m, 1H) 3.76-3.88 (m, 3H) 3.64 (d, J=14.31 Hz, 1H) 3.29 (br. s., 1H) 3.16 (d, J=14.31 Hz, 1H) 2.87-3.06 (m, 3H) 2.35 (d, J=2.76 Hz, 1H) 1.70-1.96 (m, 2H) 1.38-1.63 (m, 2H). MS: LC/MS RT=0.923 mins [M+H]=345.08.

Workup

  1. temperatureThe reaction was then heated an additional 2 hours
  2. temperaturecooled to room temperature
  3. customthe organic was collected
  4. customdried to a residue
  5. extractionThe neutralized layer was extracted in chloroform
  6. customthe chloroform was removed in vacco
  7. customto give a crude mixture
  8. customThis mixture was purified by PREP HPLC
  9. additiondiluted with saturated sodium bicarbonate
  10. extractionThe solution was then extracted several times with chloroform
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e35cc16df0154ddca993f433491a6319
Source dataset
uspto-grants-2013_08
Patent number
US08507516B2

Reaction notes

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