Triphenylphosphine → N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide

HRID 403036Notes

Reaction equation

HRID 403036 reaction equation
[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:22])[C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)[CH:7]=2)[CH2:3][CH2:2]1.[O:24]1[CH2:28][CH2:27][O:26][CH:25]1[CH2:29][O:30][C:31]1[CH:32]=[CH:33][C:34]([CH2:37]O)=[N:35][CH:36]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:22])[C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:37][C:34]4[CH:33]=[CH:32][C:31]([O:30][CH2:29][CH:25]5[O:26][CH2:27][CH2:28][O:24]5)=[CH:36][N:35]=4)=[CH:19][CH:20]=3)[CH:7]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 66630733[5-(1,3-Dioxolan-2-ylmethoxy)-pyridin-2-yl]methanolHCID 66631169N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide

Product 1

HCID 11488985N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamideYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide (3.1 g, 10 mmol) in dry THF (200 mL) at 25° C. was added [5-(1,3-dioxolan-2-ylmethoxy)-pyridin-2-yl]methanol (2.4 g, 11 mmol), triphenylphosphine (2.9 g, 11 mmol) and di-tert-butyl azodicarboxylate (2.6 g, 11 mmol). The solution was stirred for 16 hours, then the solvent was evaporated and the residue dissolved in ethyl acetate/methanol (19:1, 50 mL) and purified by chromatography on silica, eluting with a gradient of 5-20% methanol in ethyl acetate, to give the title compound as a white solid (3.8 g, 76%). NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.68 (m, 2H), 2.24 (s, 3H), 2.84 (m, 1H), 3.85 (m, 2H), 3.92 (m, 2H), 4.10 (m, 2H), 5.20 (m, 3H), 7.12 (d, 2H), 7.30 (d, 1H), 7.45 (s, 2H), 7.62 (dd, 1H), 7.78 (s, 1H), 7.95 (d, 2H), 8.30 (s, 1H), 8.35 (d, 1H), 9.80 (s, 1H); Mass Spectrum: M+H+ 504.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe residue dissolved in ethyl acetate/methanol (19:1, 50 mL)
  3. custompurified by chromatography on silica
  4. washeluting with a gradient of 5-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-a94af42d91254efebff705b4a63a6e46
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Reaction notes

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