Acetic Acid → HCID 178491053, compound

HRID 1502447Notes

Reaction equation

HRID 1502447 reaction equation
[F:1][C@H:2]1[CH2:4][C@H:3]1[C:5]([NH:7][C:8]1[N:9]=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[C:13]([C:18]1[CH:19]=[N:20][C:21]([C:25](O)(O)[C:26]([F:29])([F:28])[F:27])=[CH:22][C:23]=1[CH3:24])[CH:12]=2)=[O:6].[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1.C(O)(=O)C>C1(C)C=CC=CC=1>[F:1][C@H:2]1[CH2:4][C@H:3]1[C:5]([NH:7][C:8]1[N:9]=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[C:13]([C:18]1[CH:19]=[N:20][C:21](/[C:25](=[N:39]/[CH2:38][C:37]3[CH:40]=[CH:41][C:34]([O:33][CH3:32])=[CH:35][CH:36]=3)/[C:26]([F:27])([F:29])[F:28])=[CH:22][C:23]=1[CH3:24])[CH:12]=2)=[O:6]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 754524-MethoxybenzylamineHCID 71115359HCID 71115359, compound

Product 1

HCID 178491053HCID 178491053, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a mixture of (1S,2S)-2-fluoro-N-(7-(4-methyl-6-(2,2,2-trifluoro-1,1-dihydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (113.8 mg; 0.2614 mmol) and toluene (2 mL) was added a scoop of oven-dried 4 angstrom molecular sieves and a premixed solution of 4-methoxybenzylamine (54 μL; 0.393 mmol) and acetic acid (23 μL; 0.401 mmol) in toluene (1 mL). The reaction mixture was then heated at 100° C. for 3 days. The reaction mixture was cooled to room temperature and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 99.7 mg of a 1:1 mixture of the title compound and unreacted starting material. LCMS (ESI): M +H=419.2.

Workup

  1. additionwas added a scoop of oven-dried 4 angstrom molecular sieves
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between dichloromethane and saturated aqueous sodium bicarbonate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane)
  8. customto yield

Sources & evidence

ORD record
ord-53f64f6595664057a396e7ae48293625
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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