Ethyl Acetate → 3-[(2-Amino-2-methyl-3-phenylpropoxy)methyl]-5-[(methylsulfonyl)(propyl)amino]benzoic acid

HRID 899473Notes

Reaction equation

HRID 899473 reaction equation
C(OC([NH:8][C:9]([CH3:37])([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([N:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:23][CH2:24][CH3:25])[CH:21]=1)[C:16]([OH:18])=[O:17])=O)(C)(C)C.CCOC(C)=O>Cl>[NH2:8][C:9]([CH3:37])([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([N:22]([S:26]([CH3:29])(=[O:28])=[O:27])[CH2:23][CH2:24][CH3:25])[CH:21]=1)[C:16]([OH:18])=[O:17]

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 588563373-({2-[(Tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoic acid2×

Product 1

HCID 673189663-[(2-Amino-2-methyl-3-phenylpropoxy)methyl]-5-[(methylsulfonyl)(propyl)amino]benzoic acid

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

3-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoic acid (intermediate XI, 15.0 mg, 0.028 mmol) was taken up in HCl(g) saturated EtOAc (1 mL). After 30 min, it was concentrated under a flow of nitrogen to give 3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-5-[(methylsulfonyl)(propyl)amino]benzoic acid as a white solid which was then taken up in DMF (800 μL) with BOP reagent (15.0 mg, 0.033 mmol), ethyl(diisopropyl)amine (12.0 μL, 0.069 mmol), and (1,1-dimethylprop-2-yn-1-yl)amine (23.0 mg, 0.276 mmol). After sitting at RT for 5 hr, the reaction was purified by preparative HPLC (5->95% CH3CN/H2O, 0.1% added TFA, C18 PRO YMC 20×150 mm) to afford 3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-N-(1,1-dimethylprop-2-yn-1-yl)-5-[(methylsulfonyl)(propyl)amino]benzamide as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.81 (br s, 3H), 7.77 (s, 1H), 7.69 (s, 1H), 7.47 (s, 1H), 7.35-7.27 (m, 3H), 7.22-7.16 (m, 2H), 6.89 (s, 1H), 4.61 (A of AB, d, J=11.7 Hz, 1H), 4.54 (B of AB, d, J=11.7 Hz, 1H), 3.64 (t, J=7.1 Hz, 2H), 3.51 (A of AB, d, J=9.8 Hz, 1H), 3.45 (B of AB, d, J=9.8 Hz, 1H), 3.17 (A of AB, d, J=13.2 Hz, 1H), 3.00 (B of AB, d, J=13.2 Hz, 1H), 2.86 (s, 3H), 1.75 (s, 6H), 1.54-1.44 (m, 2H), 1.32 (s, 3H), 1.27 (s, 3H), 0.89 (t, J=7.3 Hz, 3H).

Workup

  1. concentrationit was concentrated under a flow of nitrogen

Sources & evidence

ORD record
ord-fab199e7133647568c33aeb2120ba36f
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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