Triphenylphosphine → 3-((3-Chloroisoquinolin-8-yl)methyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920248Notes

Reaction equation

HRID 920248 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[C:19]([F:20])=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].[Cl:32][C:33]1[N:34]=[CH:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][C:37]=2[CH2:43]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O>C1COCC1>[Cl:32][C:33]1[N:34]=[CH:35][C:36]2[C:41]([CH:42]=1)=[CH:40][CH:39]=[CH:38][C:37]=2[CH2:43][N:14]1[C:13]2[CH:18]=[C:19]([F:20])[C:10]([S:7]([NH:6][C:21]3[S:25][N:24]=[CH:23][N:22]=3)(=[O:9])=[O:8])=[CH:11][C:12]=2[O:16][C:15]1=[O:17]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 89524955(3-Chloroisoquinolin-8-yl)methanolHCID 89525954N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 715566793-((3-Chloroisoquinolin-8-yl)methyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (11-3) and (3-chloroisoquinolin-8-yl)methanol in THF (697 μl) at 0° C. was treated with ps-triphenylphosphine (73.1 mg, 0.279 mmol) (152 mg resin-bound PPh3, 1.84 mmol PPh3/g of resin), then (E)-di-tert-butyl diazene-1,2-dicarboxylate (64.2 mg, 0.279 mmol). Reaction mixtured was monitored at 0° C. After stirring at 0° C. for 2 h, the reaction was filtered and concentrated in vacuo. Residue was dissolved in 1 mL of DCM and treated with 0.25 mL of TFA. After stirring at RT for 30 minutes, the solvent and TFA were removed in vacuo. Purified by reverse phase chromatography (10-95% MeCN in water w/0.1% TFA, C18 column) to yield 25-2. 1H NMR δ (ppm)(CH3OH-d4): 9.48 (1H, s), 8.20 (1H, s), 7.96 (1H, s), 7.90 (1H, d, J=8.36 Hz), 7.81 (1H, d, J=5.48 Hz), 7.75 (1H, t, J=7.75 Hz), 7.57 (1H, d, J=7.08 Hz), 7.12 (1H, d, J=9.32 Hz), 5.69 (2H, s). HRMS [M+H]C19H11ClFN5O4S2 calc'd 491.9998. Found 492.0001.

Workup

  1. customReaction
  2. custommixtured was monitored at 0° C
  3. filtrationthe reaction was filtered
  4. concentrationconcentrated in vacuo
  5. dissolutionResidue was dissolved in 1 mL of DCM
  6. additiontreated with 0.25 mL of TFA
  7. stirringAfter stirring at RT for 30 minutes
  8. customthe solvent and TFA were removed in vacuo
  9. customPurified by reverse phase chromatography (10-95% MeCN in water w/0.1% TFA, C18 column)
  10. customto yield 25-2

Sources & evidence

ORD record
ord-2223f13bc5454a239b879e4451253fb5
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

Loading…