Triphenylphosphine → (R)-3-(1-(Isoquinolin-8-yl)ethyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920230Notes

Reaction equation

HRID 920230 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:20]1[S:24][N:23]=[CH:22][N:21]=1)[S:7]([C:10]1[CH:19]=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].[CH:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][C:39]=2[C@@H:41](O)[CH3:42])[CH:34]=[CH:33][N:32]=1.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>[CH:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][C:39]=2[C@H:41]([N:14]2[C:13]3[CH:18]=[CH:19][C:10]([S:7]([NH:6][C:20]4[S:24][N:23]=[CH:22][N:21]=4)(=[O:8])=[O:9])=[CH:11][C:12]=3[O:16][C:15]2=[O:17])[CH3:42])[CH:34]=[CH:33][N:32]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 89524783(S)-1-(isoquinolin-8-yl)ethanolHCID 89526027N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 89526180(R)-3-(1-(Isoquinolin-8-yl)ethyl)-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)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (100 mg, 0.214 mmol) and (S)-1-(isoquinolin-8-yl)ethanol (74.3 mg, 0.429 mmol) in THF (1072 μl) at 0° C. was treated with PS-triphenylphosphine (112 mg, 0.429 mmol) (0.233 g resin-bound PPh3, 1.84 mmol PPh3/g of resin), and (E)-di-tert-butyl diazene-1,2-dicarboxylate (99 mg, 0.429 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 14-7. 1H NMR δ (ppm)(CH3OH-d4): 9.86 (1H, s), 8.61 (1H, d, J=6.42 Hz), 8.47 (2H, dd, J=14.05, 6.52 Hz), 8.32-8.24 (2H, m), 8.14 (1H, s), 7.64-7.57 (2H, m), 7.29 (1H, d, J=8.39 Hz), 6.64-6.55 (1H, m), 2.15 (3H, d, J=7.05 Hz). HRMS [M+H]C20H15N5O4S2 calc'd 454.0638. Found 454.0633.

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 14-7

Sources & evidence

ORD record
ord-2d882191c59a41fe9bbcd3257795d5e7
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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