Dimethylformamide → [3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanone

HRID 1891021Notes

Reaction equation

HRID 1891021 reaction equation
C(OC([N:11]1[C:19]2[C:14](=[CH:15][C:16]([C:21]([N:23]3[CH2:28][CH2:27][CH:26]([CH2:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)[CH2:25][CH2:24]3)=[O:22])=[C:17]([Cl:20])[CH:18]=2)[C:13]([C:37](=O)[CH3:38])=[CH:12]1)=O)C1C=CC=CC=1.Cl.[CH3:41][C:42]([CH3:47])([CH3:46])[C:43]([NH2:45])=[NH:44].[CH3:48]N(C)C=O>>[C:42]([C:43]1[N:45]=[C:37]([C:13]2[C:14]3[C:19](=[CH:18][C:17]([Cl:20])=[C:16]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([CH2:29][C:30]5[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=5)[CH2:25][CH2:24]4)=[O:22])[CH:15]=3)[NH:11][CH:12]=2)[CH:38]=[CH:48][N:44]=1)([CH3:47])([CH3:46])[CH3:41]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 2781880Propanimidamide, 2,2-dimethyl-, hydrochloride (1:1)HCID 677744473-Acetyl-6-chloro-5-[4-(4-fluoro-benzyl)-piperidine-1-carbonyl]-indole-1-carboxylic acid benzyl ester

Product 1

HCID 57325406[3-(2-tert-Butyl-pyrimidin-4-yl)-6-chloro-1H-indol-5-yl]-[4-(4-fluorobenzyl)-piperidin-1-yl]-methanoneYield 9%

Conditions

Temperature
75 °C

Procedure

To a solution of 3-Acetyl-6-chloro-5-[4-(4-fluoro-benzyl)-piperidine-1-carbonyl]-indole-1-carboxylic acid benzyl ester (150 mg, 0.27 mmol) in N,N-dimethylformamide (1 mL) was added dimethylformamide (N,N)-di-tert-butyl acetal (0.5 mL, 2.1 mmol) and the solution was heated to 75° C. for 5 h. The material was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. This material was filtered and concentrated to give an orange oil. This was dissolved in N,N-dimethylformamide (1 mL), added 2,2,2-trimethylacetamidine hydrochloride 85° C. for 18 h. The slurry was cooled to ambient temp and partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The material was filtered and concentrated to an orange oil and purified by silica gel chromatography using ethyl acetate/heptane to afford the title compound as a yellow semi-solid (12.1 mg, 9%). MH+, m/z=505.

Workup

  1. temperatureThe material was cooled to ambient temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThis material was filtered
  6. concentrationconcentrated
  7. customto give an orange oil
  8. temperatureThe slurry was cooled to ambient temp
  9. custompartitioned between ethyl acetate and water
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationThe material was filtered
  13. concentrationconcentrated to an orange oil
  14. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-f36304d5d579470e8243ee59991043c9
Source dataset
uspto-grants-2013_08
Patent number
US08507499B2

Reaction notes

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