Water → (S)-7-(1-Aminoethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

HRID 58251Notes

Reaction equation

HRID 58251 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13](=[O:14])[N:12]3[C:15]([CH3:18])=[CH:16][S:17][C:11]3=[N:10][C:9]=2[C@@H:19]([NH:21]C(=O)OC(C)(C)C)[CH3:20])[CH:5]=[CH:6][CH:7]=1.O1CCOCC1.O.[OH-].[Na+]>Cl>[NH2:21][C@H:19]([C:9]1[N:10]=[C:11]2[S:17][CH:16]=[C:15]([CH3:18])[N:12]2[C:13](=[O:14])[C:8]=1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 58111443HCID 58111443, compound

Product 1

HCID 58111427(S)-7-(1-Aminoethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-oneYield 105.6%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

(S)-tert-Butyl 1-(6-(3-fluorophenyl)-3-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-7-yl)ethylcarbamate (4.15 g, 10.3 mmol) was dissolved in a 4.0 M solution of hydrogen chloride in 1,4-dioxane (25.7 mL, 102.8 mmol) and the solution was stirred at room temperature for 45 min. HPLC indicated that the reaction was complete. To the solution was added water (10 mL) followed by 3 N aqueous sodium hydroxide solution at 0-5° C. to adjust the pH to 10. The aqueous mixture was extracted with ethyl acetate (2×30 mL). The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give (S)-7-(1-Aminoethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (3.30 g, 10.88 mmol, 103% yield). LCMS calculated for C15H15FN3OS (M+H)+: m/z 304.08. Found 303.9. 1H NMR (400 MHz, DMSO-d6) δ 7.45 (ddd, J=8.1, 7.9, 5.9 Hz, 1H), 7.19 (m, 1H), 7.12 (m, 2H) 7.04 (q, J=1.1 Hz, 1H), 3.57 (q, J=6.6 Hz, 1H), 2.64 (d, J=1.3 Hz, 3H), 1.10 (d, J=6.7 Hz, 3H)

Workup

  1. extractionThe aqueous mixture was extracted with ethyl acetate (2×30 mL)
  2. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f58268fa71514d6dbdd5ff5f275c90fb
Source dataset
uspto-grants-2016_09
Patent number
US09434746B2

Reaction notes

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