Hydrochloric Acid → HCID 52935511, compound

HRID 1891116Notes

Reaction equation

HRID 1891116 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([N:13]1[CH:17]=[CH:16]N=C1)=S.[CH:18](N=C=NC(C)C)([CH3:20])[CH3:19].C(Cl)(Cl)Cl.[OH2:31].Cl.[CH3:33][N:34]([CH:36]=O)[CH3:35]>O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[O:31][C@:16]2([CH2:35][N:34]3[CH2:36][C@@H:19]2[CH2:18][CH2:20][CH2:33]3)[CH2:17][N:13]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 19703709N-(benzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamideHCID 22418719Chloroform water2×

Product 1

HCID 52935511HCID 52935511, compoundYield 13%

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-(benzo[d]thiazol-2-yl)-1H-imidazole-1-carbothioamide (550 mg, 2.12 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 with chloroform and the chloroform was removed in vacuo 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 (5S*,5′R*)—N-(benzo[d]thiazol-2-yl)-4′H-1-azaspiro[bicyclo[3.2.1]octane-6,5′-oxazol]-2′-amine as a white powder (45.1 mg, 13%) 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.17-9.65 (m, 1H) 7.62 (dd, J=13.18, 7.65 Hz, 2H) 7.25-7.37 (m, 1H) 7.11-7.20 (m, 1H) 4.12 (d, J=9.79 Hz, 1H) 3.96-4.06 (m, 1H) 3.59 (d, J=14.31 Hz, 1H) 3.24 (d, J=11.54 Hz, 1H) 3.12 (dd, J=14.31, 2.51 Hz, 1H) 2.79-3.00 (m, 3H) 2.30 (q, J=3.35 Hz, 1H) 1.71-1.92 (m, 2H) 1.33-1.57 (m, 2H) LC/MS RT=0.687 rains [M+H]=315.06.

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 with chloroform
  6. customthe chloroform was removed in vacuo
  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-59737f3304e84681bf6b10614393ad25
Source dataset
uspto-grants-2013_08
Patent number
US08507516B2

Reaction notes

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