4-Methoxybenzylamine → HCID 89906624, compound

HRID 525742Notes

Reaction equation

HRID 525742 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([C:13]([NH:15][CH2:16][C:17]#[CH:18])=O)=[CH:11][C:10]([C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)=[O:20])=[CH:9][N:8]=2)[CH2:3]1.[CH3:33][O:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH2:40])=[CH:37][CH:36]=1>C1(C)C=CC=CC=1.FC(F)(F)S([O-])(=O)=O.[Zn+2].FC(F)(F)S([O-])(=O)=O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([C:13]3[N:40]([CH2:39][C:38]4[CH:41]=[CH:42][C:35]([O:34][CH3:33])=[CH:36][CH:37]=4)[C:17]([CH3:18])=[CH:16][N:15]=3)=[CH:11][C:10]([C:19]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:31])([F:30])[F:32])=[CH:26][CH:27]=3)=[O:20])=[CH:9][N:8]=2)[CH2:3]1

Participants

5

Reactant 2

HCID 754524-MethoxybenzylamineHCID 89907813HCID 89907813, compound

Product 1

HCID 89906624HCID 89906624, compound

Reagents, catalysts & solvents 2

HCID 104671Zinc trifluoromethanesulfonateCatalystHCID 1140TolueneSolvent

Procedure

A stirred mixture of (R)-2-(3-hydroxypyrrolidin-1-yl)-N3-(prop-2-yn-1-yl)-N5-(4-(trifluoromethoxy)phenyl)pyridine-3,5-dicarboxamide (Stage 72.2, 0.50 g, 1.115 mmol) and 4-methoxybenzylamine (0.175 mL, 1.338 mmol) in toluene (30 mL) was treated with zinc trifluoromethanesulphonate (61 mg, 0.17 mmol) and heated under reflux for 41 h. The solvent was evaporated off under reduced pressure and the crude product was purified by flash chromatography (RediSep® Silica gel column, EtOAc 100%) to afford the title compound as a foam. HPLC (Condition 4) tR=4.66 min, UPLC-MS (Condition 8) tR=0.93 min, m/z=568.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 1.72 (br. s, 1H), 2.19 (s, 3H), 2.74-3.09 (m, 2H), 2.85-3.07 (m, 1H), 3.15-3.31 (m, 2H), 3.64 (s, 3H), 4.15 (br. s, 1H), 4.90 (m, 3H), 6.72-6.86 (m, 5H), 7.35 (d, J=8.59 Hz, 2H), 7.85 (d, J=8.42 Hz, 2H), 7.19-8.03 (m, 1H), 8.78 (br. s, 1H), 10.05-10.20 (m, 1H).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 41 h
  3. customThe solvent was evaporated off under reduced pressure
  4. customthe crude product was purified by flash chromatography (RediSep® Silica gel column, EtOAc 100%)

Sources & evidence

ORD record
ord-e293d7b1799c499ea7c65035c755634e
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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