tert-Butanol → HCID 86707733, compound

HRID 1190839Notes

Reaction equation

HRID 1190839 reaction equation
[S:1](Cl)([N:4]=C=O)(=[O:3])=[O:2].CC(O)(C)C.[NH2:13][C@@H:14]([CH2:25][C:26]1[O:27][C:28]([CH2:31][C:32]2[S:33][C:34]3[CH:40]=[C:39]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH:38]=[CH:37][C:35]=3[N:36]=2)=[N:29][N:30]=1)[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16]>C(Cl)Cl>[C:41]1([C:39]2[CH:38]=[CH:37][C:35]3[N:36]=[C:32]([CH2:31][C:28]4[O:27][C:26]([CH2:25][C@H:14]([NH:13][S:1](=[O:3])(=[O:2])[NH2:4])[C:15]([O:17][CH2:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)=[O:16])=[N:30][N:29]=4)[S:33][C:34]=3[CH:40]=2)[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 70918Chlorosulfonyl isocyanateHCID 86707732HCID 86707732, compound

Product 1

HCID 86707733HCID 86707733, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of Compound 45a (460 mg, 0.81 mmol) in DCM (5 mL) was added TFA (5 mL) and the reaction mixture stirred for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue was co-evaporated with toluene (3×) and DCM, then dried under high vacuum to give (S)-benzyl 2-amino-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (500 mg, 100% yield) as a yellow solid. LCMS=1.90 min using analytical method (B), 471.0 (M+H). In a separate flask, to a solution of sulfurisocyanatidic chloride (170 mg, 1.2 mmol) in DCM (2 mL) was added 2-methylpropan-2-ol (90 mg, 1.2 mmol) in DCM (2 mL) and the reaction mixture stirred for 20 min. The resulting solution was then added to a mixture of (S)-benzyl 2-amino-3-(5-((6-phenylbenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)propanoate (500 mg, 0.81 mmol) and TEA (0.56 mL, 4.0 mmol) in DCM (5 mL) and the reaction mixture stirred for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in EtOAc, washed with 1 N HCl solution and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was dissolved in DCM (6 mL) and treated with TFA (3 mL) then stirred for 1 h. The mixture was concentrated under reduced pressure, co-evaporated under reduced pressure with toluene and DCM, and the residue purified by silica gel chromatography eluting with 0-10% MeOH/DCM to give Compound 45b (380 mg, 86% yield) as a yellow solid. LCMS=2.00 min using analytical method (B), 550.2 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.15-8.08 (m, 1H), 8.06-8.00 (m, 1H), 7.76-7.70 (m, 1H), 7.66-7.58 (m, 2H), 7.50-7.44 (m, 2H), 7.42-7.27 (m, 7H), 5.65-5.58 (m, 1H), 5.23-5.19 (m, 1H), 5.16-5.09 (m, 2H), 4.73-4.61 (m, 3H), 3.53-3.30 (m, 2H).

Workup

  1. customLCMS=1.90 min
  2. stirringthe reaction mixture stirred for 3 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in EtOAc
  5. washwashed with 1 N HCl solution and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in DCM (6 mL)
  10. additiontreated with TFA (3 mL)
  11. stirringthen stirred for 1 h
  12. concentrationThe mixture was concentrated under reduced pressure
  13. customthe residue purified by silica gel chromatography
  14. washeluting with 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-edc75ebd0e384915a6feaeda4b414a60
Source dataset
uspto-grants-2014_03
Patent number
US08680090B2

Reaction notes

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