Triphenylphosphine → 2-Oxo-N-(1,2,4-thiadiazol-5-yl)-3-((2-(2,2,2-trifluoroethyl)-1,2,3,4 tetrahydroisoquinolin-8-yl)methyl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920223Notes

Reaction equation

HRID 920223 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].[F:31][C:32]([F:47])([F:46])[CH2:33][N:34]1[CH2:43][CH2:42][C:41]2[C:36](=[C:37]([CH2:44]O)[CH:38]=[CH:39][CH:40]=2)[CH2:35]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:17]=[C:15]1[N:14]([CH2:44][C:37]2[CH:38]=[CH:39][CH:40]=[C:41]3[C:36]=2[CH2:35][N:34]([CH2:33][C:32]([F:47])([F:31])[F:46])[CH2:43][CH2:42]3)[C:13]2[CH:18]=[CH:19][C:10]([S:7]([NH:6][C:20]3[S:24][N:23]=[CH:22][N:21]=3)(=[O:8])=[O:9])=[CH:11][C:12]=2[O:16]1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 89526014(2-(2,2,2-Trifluoroethyl)-1,2,3,4-tetrahydroisoquinolin-8-yl)methanolHCID 89526027N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 1176292832-Oxo-N-(1,2,4-thiadiazol-5-yl)-3-((2-(2,2,2-trifluoroethyl)-1,2,3,4 tetrahydroisoquinolin-8-yl)methyl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-5 (16.5 mg, 0.037 mmol) and 7-5 (9.02 mg, 0.037 mmol) in THF (368 μl) at RT was treated with PS-bound triphenylphosphine (1.84 mmol/g, 40.2 mg, 0.074 mmol), and DTBAD (16.94 mg, 0.074 mmol). After 30 min, LCMS showed complete consumption of SM. Filtered through Celite and concentrated in vacuo. Dissolved in 245 uL DCM, 123 uL TFA and stirred at RT. After 30 min, diluted with 1 mL MeOH, filtered through Celite and washed with 1 mL MeOH. Concentrated in vacuo and purified by reverse-phase HPLC (C18 column, 5-70% 0.1% TFA/CH3CN:0.1% TFA/H2O) to give 7-6 as an off-white solid. 1H NMR δ (ppm) (DMSO-d6): 8.48 (1H, s), 7.78 (1H, d, J=1.69 Hz), 7.67 (1H, dd, J=8.28, 1.72 Hz), 7.25 (1H, d, J=8.33 Hz), 7.14-7.09 (2H, m), 6.92 (1H, d, J=6.83 Hz), 5.00 (2H, s), 3.99 (3H, s), 3.54 (3H, d, J=12.20 Hz), 2.90 (2H, s). HRMS C21H19F3N5O4S2 [M+H] calc 526.0825, obs. 526.0806.

Workup

  1. customconsumption of SM
  2. filtrationFiltered through Celite
  3. concentrationconcentrated in vacuo
  4. dissolutionDissolved in 245 uL DCM
  5. waitAfter 30 min
  6. additiondiluted with 1 mL MeOH
  7. filtrationfiltered through Celite
  8. washwashed with 1 mL MeOH
  9. concentrationConcentrated in vacuo
  10. custompurified by reverse-phase HPLC (C18 column, 5-70% 0.1% TFA/CH3CN:0.1% TFA/H2O)

Sources & evidence

ORD record
ord-c59ca463e4544dfc9c4ba55f2d32040a
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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