Tert-Butyl nitrite → HCID 89761998, compound

HRID 528555Notes

Reaction equation

HRID 528555 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]3[CH:14]=[C:15]([S:18]([N:21]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)[C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:20])=[O:19])[CH:16]=[CH:17][C:9]2=3)=[C:4]([Br:36])[CH:3]=1.N(OC(C)(C)C)=O.[N:44]([Si](C)(C)C)=[N+:45]=[N-]>C(#N)C>[N:1]([C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]3[CH:14]=[C:15]([S:18]([N:21]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)[C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:20])=[O:19])[CH:16]=[CH:17][C:9]2=3)=[C:4]([Br:36])[CH:3]=1)=[N+:44]=[N-:45]

Participants

5

Reactant 3

HCID 10906Tert-Butyl nitriteHCID 78378AzidotrimethylsilaneHCID 89761746HCID 89761746, compound

Product 1

HCID 89761998HCID 89761998, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(4-amino-2-bromophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.095 g, 0.162 mmol) in dry acetonitrile (1.617 mL) at 0° C. was added tert-butyl nitrite (0.027 mL, 0.226 mmol), followed by dropwise addition of azidotrimethylsilane (0.026 mL, 0.194 mmol). The resulting mixture was stirred for 20 minutes at RT. The reaction was concentrated under a vacuum, and purified via silica gel MPLC, eluting with a gradient of 0% to 100% ethyl acetate in heptanes to provide 4-(4-azido-2-bromophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as tan solid. The material was taken up in DCM (1.5 mL), and TFA (0.125 mL, 1.617 mmol) was added. The reaction was stirred at RT for 1.5 h, after which the reaction was concentrated under a vacuum. The material was purified by reverse-phase preparative HPLC using a Phenomenex Luna column, 5 micron, C18(2), 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 30% to 90% over 20 min to provide 4-(4-azido-2-bromophenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide 2,2,2-trifluoroacetate (0.0308 g, 0.051 mmol) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.55-3.63 (m, 1 H) 3.64-3.72 (m, 1 H) 4.27-4.34 (m, 1 H) 4.35-4.41 (m, 1 H) 6.10 (d, J=8.41 Hz, 1 H) 6.78 (d, J=4.69 Hz, 1H) 7.08-7.15 (m, 2 H) 7.22 (d, J=4.60 Hz, 1 H) 7.28 (dd, J=8.51, 2.54 Hz, 1 H) 7.53 (d, J=8.51 Hz, 1 H) 7.56 (d, J=2.54 Hz, 1 H) 12.55 (br. s., 1 H). m/z (ESI) 493.0 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated under a vacuum
  2. custompurified via silica gel MPLC
  3. washeluting with a gradient of 0% to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-e4da47d9e38841cfa63c7d72608b9333
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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