tert-Butanol → HCID 77844066, compound

HRID 1523778Notes

Reaction equation

HRID 1523778 reaction equation
C(O)(C)(C)C.Cl[S:7]([N:10]=C=O)(=[O:9])=[O:8].C(OC(NS(Cl)(=O)=O)=O)(C)(C)C.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]1[CH:37]=[CH:36][C:35]([C:38]2[N:39]=[CH:40][C:41]([NH2:44])=[N:42][CH:43]=2)=[C:34]([F:45])[CH:33]=1.C(N(CC)CC)C>C(Cl)Cl>[NH2:44][C:41]1[N:42]=[CH:43][C:38]([C:35]2[CH:36]=[CH:37][C:32]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[NH:25][S:7]([NH2:10])(=[O:9])=[O:8])=[CH:33][C:34]=2[F:45])=[N:39][CH:40]=1

Participants

7

Reactant 5

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 15677406tert-butyl N-(chlorosulfonyl)carbamateHCID 90314330HCID 90314330, compound

Product 1

HCID 77844066HCID 77844066, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butanol (13 mg, 0.18 mmol) in DCM (5 mL) was added chlorosulfonylisocyanate (25 mg, 0.18 mmol) at 0° Celsius. The resulting solution containing N-(tert-butoxycarbonyl)sulfamoyl chloride was added to a reaction flask containing 5-(2′-amino-3-fluorobiphenyl-4-yl)pyrazin-2-amine (50 mg, 0.18 mmol) and triethylamine (36 mg, 0.36 mmol) in anhydrous DCM (10 mL) at 0° Celsius. The mixture was warmed to rt, stirred 2 hours, then concentrated to dryness, re-dissolved in TFA/DCM (5 mL/5 mL), stirred at rt for 1 hour, and concentrated to dryness. The residue was diluted with water (10 mL) and saturated NaHCO3(aq) (10 mL), extracted with DCM (10 mL×3) and the combined organic extracts washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by HPLC to give the title compound (10 mg, 16%). MS (ESI): mass calcd. for C16H14FN5O2S, 359.09; m/z found, 360.0 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.33 (s, 1H), 8.04 (d, J=1.3, 1H), 7.91 (m, 1H), 7.63 (d, J=7.8, 1H), 7.44-7.22 (m, 4H), 7.24 (m, 1H), 7.05 (s, 2H), 6.70 (s, 2H).

Workup

  1. additionwas added to a reaction flask
  2. concentrationconcentrated to dryness
  3. dissolutionre-dissolved in TFA/DCM (5 mL/5 mL)
  4. stirringstirred at rt for 1 hour
  5. concentrationconcentrated to dryness
  6. additionThe residue was diluted with water (10 mL) and saturated NaHCO3(aq) (10 mL)
  7. extractionextracted with DCM (10 mL×3)
  8. washthe combined organic extracts washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-ddd62df388454b64ab4934fb7033f05b
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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