Triphenylphosphine → HCID 71086212, compound

HRID 528988Notes

Reaction equation

HRID 528988 reaction equation
[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:38])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[C:39]1[C:40]([C:54]([O:56][CH2:57][CH3:58])=[O:55])=[N:41][N:42]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:43]=1[CH2:44][CH2:45][CH2:46][CH3:47])=[O:16])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>C1COCC1>[NH2:1][CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:38])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[C:39]1[C:40]([C:54]([O:56][CH2:57][CH3:58])=[O:55])=[N:41][N:42]([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[C:43]=1[CH2:44][CH2:45][CH2:46][CH3:47])=[O:16]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 71086366HCID 71086366, compound

Product 1

HCID 71086212HCID 71086212, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To the solution of ethyl 4-(2-((S)-3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-butyl-1-phenyl-1H-pyrazole-3-carboxylate (60 mg, 0.075 mmol, Example 261) in THF (2.0 mL) was added triphenylphosphine (59 mg, 0.226 mmol) followed by 0.2 ml of 1N NaOH. The reaction mixture was stirred at 50° C. for 2 h. The reaction mixture was quenched with sat. aq. sodium bicarbonate solution and then extracted with EtOAc. The organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Isco 40 g column eluting with 0-15% methanol/DCM). The residue was lyophilized from acetonitrile/water to give the title compound (29 mg, 50%). 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.60 (s, 1H), 8.32 (s, 1H), 8.19-7.91 (m, 5H), 7.58-7.34 (m, 8H), 7.21-7.00 (m, 3.5H), 6.79-6.78 (m, 0.5H), 5.21-5.20 (m, 0.5H), 4.74-4.70 (m, 0.5H), 4.43-4.10 (m, 3H), 3.75-3.74 (m, 0.5H), 3.62-3.60 (m, 0.5H), 3.01-3.00 (m, 2H), 2.75-2.48 (m, 4H), 1.13-0.92 (m, 4H), 0.99 (t, J=8 Hz, 3H), 0.57-0.54 (m, 3H); MS(ESI+) m/z 770.5 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with sat. aq. sodium bicarbonate solution
  2. extractionextracted with EtOAc
  3. dry with materialThe organic extracts were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (Isco 40 g column eluting with 0-15% methanol/DCM)

Sources & evidence

ORD record
ord-4bc4a07026974058aff4fe114a9a2977
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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