Diisopropylethylamine → HCID 86612066, compound

HRID 899471Notes

Reaction equation

HRID 899471 reaction equation
[C:1]([O:5][C:6]([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:18]=[C:17]([N:19]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:20][CH2:21][CH3:22])[N:16]=[C:15]([C:27]([OH:29])=O)[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[F:47][C:48]1[CH:53]=[CH:52][C:51]([CH:54]([NH2:56])[CH3:55])=[CH:50][CH:49]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:30]([C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])([CH3:37])[CH2:10][O:11][CH2:12][C:13]1[CH:18]=[C:17]([N:19]([S:23]([CH3:26])(=[O:24])=[O:25])[CH2:20][CH2:21][CH3:22])[N:16]=[C:15]([C:27]([NH:56][CH:54]([C:51]2[CH:52]=[CH:53][C:48]([F:47])=[CH:49][CH:50]=2)[CH3:55])=[O:29])[CH:14]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1230631-(4-Fluorophenyl)ethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 58856342HCID 58856342, compound2×

Product 1

HCID 86612066HCID 86612066, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylic acid (10 mg, 0.019 mmol, intermediate VII) in DMF (0.5 mL) was added diisopropylethyl amine (0.05 mL, 0.028 mmol), [1-(4-fluorophenyl)ethyl]amine (0.008 mL, 0.056 mmol) and BOP reagent (10 mg, 0.022 mmol), and the reaction mixture was allowed to stand at rt for 40 min, purified by preparative HPLC (5->95% CH3CN/H2O, 0.1% added TFA, C18 PRO YMC 20×150 mm) to afford tert-butyl [1-benzyl-2-({2-({[1-(4-fluorophenyl)ethyl]amino}carbonyl)-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate. Boc removal in HCl(g) saturated EtOAc and lyophilization from dioxane/water provided 4-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-N-[1-(4-fluorophenyl)ethyl]-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxamide as an hydrochloride white solid. 1H NMR (400 MHz, CD3OD) δ 8.61 (d, J=8.0 Hz, 1H), 7.97 (s, 1H), 7.65 (s, 1H), 7.46-7.41 (m, 2H), 7.38-7.25 (m, 3H), 7.24-7.19 (m, 2H), 7.11-7.03 (m, 2H), 5.30-5.20 (m, 1H), 4.75 (s, 2H), 4.03-3.94 (m, 2H), 3.51 (A of AB, d, J=10.4 Hz, 1H), 3.46 (B of AB, d, J=10.4 Hz, 1H), 3.11 (A of AB, d, J=13.6 Hz, 1H), 3.10 (s, 3H), 2.92 (B of AB, d, J=13.6 Hz, 1H), 1.64-1.54 (m, 2H), 1.62 (d, J=7.2 Hz, 3H), 1.29 (s, 3H), 0.92 (t, J=7.6 Hz, 3H). HRMS (ES, M+H) calcd. for C29H37FN4O4S: 557.2593, found: 557.2613.

Workup

  1. custompurified by preparative HPLC (5->95% CH3CN/H2O, 0.1%
  2. additionadded TFA

Sources & evidence

ORD record
ord-35ced6e441524901b04babe3ec938f62
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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