Sodium hydride → HCID 58338018, compound

HRID 1409296Notes

Reaction equation

HRID 1409296 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:21])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][NH:11][C:12]1[C:13]2[N:20]=[CH:19][S:18][C:14]=2[N:15]=[CH:16][N:17]=1.F[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=1.[H-].[Na+]>CN(C=O)C.O.Cl>[CH3:1][C:2]1[CH:3]=[C:4]([O:21][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][NH:11][C:12]1[C:13]2[N:20]=[CH:19][S:18][C:14]=2[N:15]=[CH:16][N:17]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 111595142-Fluoro-4-(trifluoromethyl)pyridineHCID 58338026HCID 58338026, compound

Product 1

HCID 58338018HCID 58338018, compoundYield 104%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3-Methyl-4-[2-(thiazolo[5,4-d]pyrimidin-7-ylamino)-ethoxy]-phenol (0.13 g, 0.43 mmol) and 2-fluoro-4-trifluoromethylpyridine (0.1 g, 0.6 mmol) were dissolved with magnetic stirring in DMF (4 mL) in a 25 mL round bottom flask equipped with a dry nitrogen line at 25° C. To the solution was added NaH (60% dispersion in oil; 60 mg, 1.5 mmol) and the reaction mixture was stirred for 2 h. The reaction was diluted with H2O (100 mL), and 2 N HCl was added to adjust the pH to 6. After 24 h, a pale brown film had formed on the flask wall. The aqueous supernatant was extracted with Et2O (2×50 mL), and the pooled aqueous fractions were combined with the brown film, and then concentrated in vacuo to yield 0.2 g of a tan semi-solid. Recrystallization from hexane afforded {2-[2-methyl-4-(4-trifluoromethylpyridin-2-yloxy)-phenoxy]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamine (Compound 9; 70 mg) as white crystals: mp 107-111° C.; 1H NMR (600 MHz, CDCl3) δ 8.78 (s, 1H), 8.53 (s, 1H), 8.29 (d, J=5.2 Hz, 1H), 7.17-7.11 (m, 1H), 7.08 (s, 1H), 6.92-6.90 (m, 2H), 6.85 (d, J=8.7 Hz, 1H), 6.56 (s, 1H), 4.29-4.20 (m, 2H), 4.11 (d, J=4.4 Hz, 2H), 2.25 (s, 3H); ESIMS m/z 448.1 ([M+H]+).

Workup

  1. customequipped with a dry nitrogen line at 25° C
  2. additionwas added
  3. waitAfter 24 h
  4. customa pale brown film had formed on the flask wall
  5. extractionThe aqueous supernatant was extracted with Et2O (2×50 mL)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c42b63ebf411469bb8e7f5907b9c5d2c
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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