Tetrahydrofuran → HCID 58869558, compound

HRID 2233089Notes

Reaction equation

HRID 2233089 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[N:19]=2)=[CH:4][CH:3]=1.C1COCC1.Cl[C:37]([CH2:39][O:40]C(=O)C)=[O:38]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([C:37](=[O:38])[CH2:39][OH:40])[CH2:27][CH2:26]3)[N:19]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 26297Acetoxyacetyl chlorideHCID 58869562HCID 58869562, compound

Product 1

HCID 58869558HCID 58869558, compound

Procedure

A solution of 4-[2-(4-Fluorophenyl)-8-methylimidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-ylpiperidin-4-ylamine (Example #H.1.1; 0.2 g, 0.5 mmol) in THF (1.1 mL, 1.4 mmol) was cooled to about 0° C. Then TEA (0.13 mL, 0.94 mmol) was added followed by acetic acid chlorocarbonylmethyl ester (0.077 g, 0.56 mmol). After about 16 h, the mixture was allowed to warm to ambient temperature and filtered, washing with MeOH. The filtrate was treated with 2.50 M aqueous sodium hydroxide (0.20 mL) at ambient temperature. After about 16 h, the mixture was treated with additional 2.50 M aqueous sodium hydroxide (0.16 mL). After about 6 h, the mixture was acidified to pH 5 using 1 N HCl. The mixture was treated with DCM and water, and the layers were separated. The aqueous layer was washed with DCM (3×20 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude material was taken up in DCM/MeOH and purified via FCC using DCM/2.5% NH4OH in MeOH (95:5) to yield the title compound as a white solid after drying (0.115 g, 50%): LC/MS (Table 1, Method b) Rt=1.6 min; MS m/z: 462.3 (M+H)+.

Workup

  1. customwas cooled to about 0° C
  2. filtrationfiltered
  3. washwashing with MeOH
  4. additionThe filtrate was treated with 2.50 M aqueous sodium hydroxide (0.20 mL) at ambient temperature
  5. waitAfter about 16 h
  6. additionthe mixture was treated with additional 2.50 M aqueous sodium hydroxide (0.16 mL)
  7. waitAfter about 6 h
  8. additionThe mixture was treated with DCM and water
  9. customthe layers were separated
  10. washThe aqueous layer was washed with DCM (3×20 mL)
  11. dry with materialThe combined organic layers were dried over MgSO4
  12. concentrationconcentrated
  13. custompurified via FCC

Sources & evidence

ORD record
ord-9d57e665a7e3413aac15fd91f577b59f
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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