Triphenylphosphine → S-(2-((1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)ethyl) ethanethioate

HRID 1747131Notes

Reaction equation

HRID 1747131 reaction equation
O[CH2:2][CH2:3][C@@:4]1([C:17]([N:19]2[CH2:28][CH2:27][C:26]3[N:25]=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[CH:22][C:21]=3[CH2:20]2)=[O:18])[CH2:8][C@H:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:5]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:66]([OH:69])(=[S:68])[CH3:67].C([O-])(O)=O.[Na+]>C1COCC1.O>[C:66](=[O:69])([S:68][CH2:2][CH2:3][C@@:4]1([C:17]([N:19]2[CH2:28][CH2:27][C:26]3[N:25]=[CH:24][C:23]([C:29]([F:32])([F:30])[F:31])=[CH:22][C:21]=3[CH2:20]2)=[O:18])[CH2:8][C@H:7]([NH:9][C:10]([O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[O:16])[CH:6]=[CH:5]1)[CH3:67]

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 5363146Diisopropyl azodicarboxylateHCID 86708129tert-butyl ((1S,4S)-4-(2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamateHCID 178418634HCID 178418634, compound

Product 1

HCID 89856405S-(2-((1S,4S)-4-((tert-butoxycarbonyl)amino)-1-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)ethyl) ethanethioate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product of Example 1, Step D (1950 mg, 3.98 mmol, 1 eq) in THF (40 mL) at rt under Ar was added triphenylphosphine (2.09 g, 7.96 mmol, 2 eq), diisopropylazodicarboxylate (1.55 mL, 7.96 mmol, 2 eq) and thioacetic acid (0.59 mL, 7.96 mmol, 2 eq). After 2 hr, water and saturated NaHCO3 were added, the aqueous was extracted with ether, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (80 g column) eluting with 30 to 60% EtOAc/heptane afforded the product of Step A. 1H NMR (CHLOROFORM-d) δ: 8.71 (s, 1H), 7.71 (s, 1H), 6.21 (dd, J=5.6, 1.7 Hz, 1H), 5.80 (dd, J=5.6, 2.0 Hz, 1H), 4.75-4.94 (m, 3H), 4.64-4.75 (m, 1H), 3.96-4.07 (m, 1H), 3.86-3.96 (m, 1H), 3.14 (t, J=5.7 Hz, 2H), 2.69-2.79 (m, 2H), 2.65 (dd, J=13.4, 8.1 Hz, 1H), 2.27 (s, 3H), 1.95-2.13 (m, 2H), 1.81-1.94 (m, 1H), 1.44 (s, 9H). Calculated for C24H30F3N3O4S: 536.2 (M+23). found: 536.2.

Workup

  1. extractionthe aqueous was extracted with ether
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (80 g column)
  5. washeluting with 30 to 60% EtOAc/heptane

Sources & evidence

ORD record
ord-ef678040c0c94aac8981a6a71b8c279b
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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