Trifluoroacetic acid → HCID 89761619, compound

HRID 528558Notes

Reaction equation

HRID 528558 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:21]2[CH2:26][CH2:25][O:24][C:23]3[CH:27]=[C:28]([S:31](=[O:48])(=[O:47])[N:32](CC4C=CC(OC)=CC=4)[C:33]4[S:34][CH:35]=[CH:36][N:37]=4)[CH:29]=[CH:30][C:22]2=3)=[C:6]([C:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH:9]=2)[CH:7]=1.N(OC(C)(C)C)=O.[N:56]([Si](C)(C)C)=[N+:57]=[N-].[C:63]([OH:69])([C:65]([F:68])([F:67])[F:66])=[O:64]>C(#N)C>[F:66][C:65]([F:68])([F:67])[C:63]([OH:69])=[O:64].[F:66][C:65]([F:68])([F:67])[C:63]([OH:69])=[O:64].[N:1]([C:2]1[CH:3]=[CH:4][C:5]([N:21]2[CH2:26][CH2:25][O:24][C:23]3[CH:27]=[C:28]([S:31]([NH:32][C:33]4[S:34][CH:35]=[CH:36][N:37]=4)(=[O:48])=[O:47])[CH:29]=[CH:30][C:22]2=3)=[C:6]([C:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]=2)[CH:7]=1)=[N+:56]=[N-:57]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10906Tert-Butyl nitrite2×HCID 78378Azidotrimethylsilane3×HCID 89761691HCID 89761691, compound

Product 1

HCID 89761619HCID 89761619, compoundYield 25.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl 4-(5-amino-2-(7-(N-(4-methoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.105 g, 0.152 mmol) in dry acetonitrile (1.522 mL) at 0° C. was added tert-butyl nitrite (0.026 mL, 0.213 mmol) followed by dropwise addition of azidotrimethylsilane (0.024 mL, 0.183 mmol). The resulting mixture was stirred for 20 minutes, at which time no conversion to the desired was observed. Additional tert-butyl nitrite (0.052 mL) and azidotrimethylsilane (0.048 mL) were added at 0° C. and the reaction was once again stirred at RT for 1 h. Conversion was observed, but starting material was still the major reaction component, so the reaction was recooled to 0° C. and 0.156 mL of t-Bu nitrite was added, followed by dropwise addition of 0.144 mL of TMS-azide. After 20 minutes at RT, the reaction was complete and was concentrated under a vacuum. DCM (1.0 mL) was added, followed by TFA (0.235 mL, 3.04 mmol), and the reaction was stirred at RT for 1 h. The material was concentrated under a vacuum and 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 25% to 90% over 20 min to provide 4-(4-azido-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide bis(2,2,2-trifluoroacetate) (0.028 g, 0.039 mmol) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30-2.44 (m, 2 H) 3.19 (m, J=5.20 Hz, 2 H) 3.47-3.56 (m, 2 H) 3.62-3.70 (m, 2 H) 4.29 (t, J=4.25 Hz, 2 H) 5.76-5.83 (m, 1 H) 6.29 (d, J=8.31 Hz, 1 H) 6.79 (d, J=4.50 Hz, 1 H) 7.02 (d, J=2.74 Hz, 1 H) 7.08-7.15 (m, 2 H) 7.17 (dd, J=8.56, 2.69 Hz, 1 H) 7.22 (d, J=4.60 Hz, 1 H) 7.38 (d, J=8.51 Hz, 1 H) 8.76 (br. s., 2 H) 12.53 (br. s., 1H); m/z (ESI) 496.0 (M+H)+.

Workup

  1. stirringthe reaction was once again stirred at RT for 1 h
  2. customwas recooled to 0° C.
  3. waitAfter 20 minutes at RT
  4. concentrationwas concentrated under a vacuum
  5. additionDCM (1.0 mL) was added
  6. stirringthe reaction was stirred at RT for 1 h
  7. concentrationThe material was concentrated under a vacuum
  8. custompurified by reverse-phase preparative HPLC
  9. customover 20 min

Sources & evidence

ORD record
ord-f90fee81e9cf42f8b8d7993da4038a43
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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