HCID 89761699, compound → HCID 71666346, compound

HRID 528533Notes

Reaction equation

HRID 528533 reaction equation
[S:1]1[C:5]([NH:6][S:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:18]([C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=4[C:29]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH:30]=4)[CH2:17][CH2:16][O:15][C:14]=3[CH:42]=2)(=[O:9])=[O:8])=[N:4][CH:3]=[N:2]1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH:32]1[CH2:31][CH:30]=[C:29]([C:20]2[CH:21]=[C:22]([C:25]([F:28])([F:27])[F:26])[CH:23]=[CH:24][C:19]=2[N:18]2[CH2:17][CH2:16][O:15][C:14]3[CH:42]=[C:10]([S:7]([NH:6][C:5]4[S:1][N:2]=[CH:3][N:4]=4)(=[O:9])=[O:8])[CH:11]=[CH:12][C:13]2=3)[CH2:34][CH2:33]1

Participants

4

Reactant 1

HCID 89761699HCID 89761699, compound

Product 1

HCID 71666346HCID 71666346, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Tert-butyl 4-(2-(7-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (EXAMPLE 5, 30 mg) was diluted with 0.5 mL of DCM and TFA (0.5 mL) was added. After 5 minutes, complete conversion to the desired deprotected product was observed. The material was concentrated under a vacuum and purified via reverse-phase HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min) to yield 4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.39 (m, J=17.50 Hz, 2 H) 3.19 (m, J=12.90 Hz, 2 H) 3.59 (m, J=3.80 Hz, 2 H) 3.65-3.71 (m, 2 H) 4.30 (m, J=4.90 Hz, 2 H) 5.88 (s, 1 H) 6.48 (d, J=8.41 Hz, 1 H) 7.11-7.19 (m, 2 H) 7.59 (d, J=8.12 Hz, 1 H) 7.63 (d, J=2.05 Hz, 1 H) 7.76 (dd, J=8.41, 1.66 Hz, 1 H) 8.39 (s, 1 H) 8.77 (br. s., 2 H). m/z (ESI) 524.0 (M+H)+.

Workup

  1. additionwas added
  2. concentrationThe material was concentrated under a vacuum
  3. custompurified via reverse-phase HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min)

Sources & evidence

ORD record
ord-c8d7899f0af9401f9eaf386729f1f0a7
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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