Acetic Acid → HCID 89762090, compound

HRID 528615Notes

Reaction equation

HRID 528615 reaction equation
COC1C=CC(C[N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=CC=1.C(O)(=O)C.[CH:33](=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O>CO.O.ClCCCl>[CH2:33]([N:20]1[CH2:19][CH2:18][O:17][C:16]2[CH:21]=[C:12]([S:9]([NH:8][C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:10])=[O:11])[CH:13]=[CH:14][C:15]1=2)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×

Product 1

HCID 89762090HCID 89762090, compoundYield 12.93%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a vial charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M) (50 mg, 0.120 mmol) was added DCE (479 n1), acetic acid (10.28 μl, 0.180 mmol) and benzaldehyde (18.24 μl, 0.180 mmol). The mixture was shaken at room temperature for 10 min prior to the addition of sodium triacetoxyborohydride (76 mg, 0.359 mmol). The mixture was shaken at rt overnight yielding product (PMB protected) as the major species. To the mixture was added TFA (100 n1) and the mixture shaken at room temperature for 1 hr then at 80° C. for 1 hr. The mixture was concentrated under reduced pressure and purified with a 25 g HP spherical silica column (15 nm spherical, Interchim) ramping DCM:MeOH (90:10) in DCM (0-50%), monitoring at 215 nm providing product which had coeluted with minor impurities (51 mg). The material was repurified with Gilson RP-HPLC dissolving in DMSO/MeOH ramping ACN in H2O (10-90%, 0.1% TFA throughout). The product containing eluents were filtered through a 2 g SCX-2 column washing with MeOH, then 2 M NH3 in MeOH. The basic wash was dried under reduced pressure and lyophilized from MeOH/H2O providing product as an off-white solid, 4-benzyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (6 mg, 0.015 mmol, 12.93% yield). 1H NMR (500 MHz, DMSO-d6) ppm 3.45-3.50 (m, 2 H) 4.23 (t, J=4.33 Hz, 2 H) 4.56 (s, 2 H) 6.68 (d, J=8.55 Hz, 1 H) 6.75 (d, J=4.49 Hz, 1 H) 7.03 (d, J=2.24 Hz, 1 H) 7.14 (dd, J=8.49, 2.08 Hz, 1 H) 7.19 (d, J=4.49 Hz, 1 H) 7.26 (d, J=7.37 Hz, 3 H) 7.31-7.36 (m, 2 H) 12.48 (br. s., 1 H). m/z (ESI) 388.2 (M+H)+.

Workup

  1. stirringThe mixture was shaken at rt overnight
  2. customyielding product (PMB protected) as the major species
  3. stirringthe mixture shaken at room temperature for 1 hr
  4. waitat 80° C. for 1 hr
  5. concentrationThe mixture was concentrated under reduced pressure
  6. custompurified with a 25 g HP spherical silica column (15 nm spherical, Interchim)
  7. customproviding product which
  8. customThe material was repurified with Gilson RP-HPLC
  9. dissolutiondissolving in DMSO/MeOH
  10. additionThe product containing eluents
  11. filtrationwere filtered through a 2 g SCX-2 column
  12. washwashing with MeOH
  13. washThe basic wash
  14. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-b5f33feb85b3403b860fa08cff7cc7ee
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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