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

HRID 920256Notes

Reaction equation

HRID 920256 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].N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:68][C:69]1[CH:70]=[CH:71][CH:72]=[C:73]2[C:78]=1[CH:77]=[N:76][C:75]([NH:79]C(=O)OC(C)(C)C)=[CH:74]2>C1COCC1>[NH2:79][C:75]1[N:76]=[CH:77][C:78]2[C:73]([CH:74]=1)=[CH:72][CH:71]=[CH:70][C:69]=2[CH2:68][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:8])=[O:9])=[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 89525954N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamideHCID 89533756tert-Butyl (8-(hydroxymethyl)isoquinolin-3-yl)carbamate

Product 1

HCID 895261383-((3-Aminoisoquinolin-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 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (11-3, 50 mg, 0.107 mmol), (E)-di-tert-butyl diazene-1,2-dicarboxylate (49.4 mg, 0.214 mmol) and triphenylphosphine (56.2 mg, 0.214 mmol) were added to a 5 mL RB flask. Then THF was added and r×n mixture was stirred at 0° C. for 10 min before addition of tert-butyl (8-(hydroxymethyl)isoquinolin-3-yl)carbamate (29.4 mg, 0.107 mmol) in THF. 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 27-5. 1H NMR δ (ppm)(DMSO-d6): 9.08 (1H, s), 7.65 (1H, d, J=5.39 Hz), 7.47 (1H, d, J=8.47 Hz), 7.34-7.26 (2H, m), 6.92 (1H, d, J=7.03 Hz), 6.65 (1H, s), 5.50 (2H, s). HRMS [M+H]C19H13FN6O4S2 calc'd 473.0496. Found 473.0499.

Workup

  1. filtrationthe reaction was filtered
  2. concentrationconcentrated in vacuo
  3. dissolutionResidue was dissolved in 1 mL of DCM
  4. additiontreated with 0.25 mL of TFA
  5. stirringAfter stirring at RT for 30 minutes
  6. customthe solvent and TFA were removed in vacuo
  7. customPurified by reverse phase chromatography (10-95% MeCN in water w/0.1% TFA, C18 column)
  8. customto yield 27-5

Sources & evidence

ORD record
ord-174d6b277a5e45beae7a7b6fc7f1ec75
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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