Sodium hydride → 5-Cyclopropyl-4-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (3-carbamoylmethyl-oxetan-3-yl)-amide

HRID 1480120Notes

Reaction equation

HRID 1480120 reaction equation
[C:1]([CH2:4][C:5]1([NH:9][C:10]([C:12]2[CH:17]=[C:16](Cl)[C:15]([CH:19]3[CH2:21][CH2:20]3)=[CH:14][N:13]=2)=[O:11])[CH2:8][O:7][CH2:6]1)(=[O:3])[NH2:2].[F:22][C:23]([F:28])([F:27])[C@H:24]([OH:26])[CH3:25].[H-].[Na+]>CN(C=O)C>[C:1]([CH2:4][C:5]1([NH:9][C:10]([C:12]2[CH:17]=[C:16]([O:26][C@H:24]([CH3:25])[C:23]([F:28])([F:27])[F:22])[C:15]([CH:19]3[CH2:21][CH2:20]3)=[CH:14][N:13]=2)=[O:11])[CH2:8][O:7][CH2:6]1)(=[O:3])[NH2:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6993809(2R)-1,1,1-trifluoropropan-2-olHCID 902149234-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid (3-carbamoylmethyl-oxetan-3-yl)-amide

Product 1

HCID 902149185-Cyclopropyl-4-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (3-carbamoylmethyl-oxetan-3-yl)-amideYield 7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid (3-carbamoylmethyl-oxetan-3-yl)-amide (Example 63b, 40 mg, 129 μmol) in dry DMF (1.5 mL) in a microwave-vial were added (R)-1,1,1-trifluoropropan-2-ol (CAN 17628-73-8, 42.1 mg, 258 μmol) and sodium hydride 60% (15.5 mg, 387 μmol) and the reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was heated to 100° C. for 30 minutes under microwave radiation. The reaction was directly purified by preparative HPLC without any work-up to yield the title compound (3.5 mg, 7.0%) as a grey solid. MS (ESI, m/z): 388.0 (M+H+).

Workup

  1. temperatureThe reaction mixture was heated to 100° C. for 30 minutes under microwave radiation
  2. customThe reaction was directly purified by preparative HPLC without any work-up

Sources & evidence

ORD record
ord-f2a0daff69e2475aa95cf34430150f1a
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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