Hydrochloric Acid → HCID 16066664, compound

HRID 1896205Notes

Reaction equation

HRID 1896205 reaction equation
Cl[C:2]1[N:3]=[C:4](Cl)[C:5]2[N:10]([CH2:11][CH2:12][O:13][CH2:14][CH3:15])[N:9]=[C:8]([CH2:16][CH3:17])[C:6]=2[N:7]=1.[NH2:19][C:20]1[CH:25]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=1.C(N(CC)C(C)C)(C)C.[NH:36]1[CH2:44][CH2:43][CH:39]([C:40]([OH:42])=[O:41])[CH2:38][CH2:37]1.Cl>C(OCC)(=O)C.O.CN1CCCC1=O>[CH2:14]([O:13][CH2:12][CH2:11][N:10]1[C:5]2[C:4]([NH:19][C:20]3[CH:25]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=3)=[N:3][C:2]([N:36]3[CH2:44][CH2:43][CH:39]([C:40]([OH:42])=[O:41])[CH2:38][CH2:37]3)=[N:7][C:6]=2[C:8]([CH2:16][CH3:17])=[N:9]1)[CH3:15]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 15332-Amino-4-methylpyridineHCID 37734-Piperidinecarboxylic acidHCID 81531DiisopropylethylamineHCID 57744535HCID 57744535, compound

Product 1

HCID 16066664HCID 16066664, compoundYield 57.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The 5,7-dichloro-1-(2-ethoxyethyl)-3-ethyl-1H-pyrazolo[4,3-d]pyrimidine prepared in step 4 (1 mmol), 2-amino-4-picoline (2 mmol), N,N-diisopropylethylamine (3 mmol), and N-methylpyrrolidone (1 mL) were added to each of two reaction vessels. Each vessel was irradiated in a CEM Discover microwave for 15 minutes at 150° C. Isonipecotic acid (3 mmol) was added to each reaction vessel and the resulting mixture irradiated for 15 minutes at 180° C. The contents of the two reaction vessels were combined. Water and ethyl acetate was added to the mixture and the mixture was shaken. Hydrochloric acid (1M) was added to the mixture and the mixture was shaken again. The layers were separated. The organic layer was washed with water, hydrochloric acid (1M) was added, and the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and evaporated. The pH of the aqueous layer was raised to about six by adding saturated sodium carbonate and the aqueous layer was then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, added to the above organic residue and evaporated. The solution was purified by RP-HPLC on a Varian Dynamax C-18 column (250×41.4 mm) with a gradient of 10-95% acetonitrile/water (hydrochloric acid) over 15 minutes in two batches. Fractions were combined and evaporated to afford 0.26 g of the title compound. 1H NMR (400 MHz, DMSO-d6): 1.10 (t, 3 H), 1.30 (t, 3 H), 1.49-1.60 (m, 2 H), 1.84-1.95 (m, 2 H), 2.32-2.36 (m, 3 H), 2.52-2.57 (m, 1 H), 2.78 (q, 2 H), 2.99-3.08 (m, 2 H), 3.52 (q, 2 H), 3.78 (t, 2 H), 4.45-4.53 (m, 2 H), 4.56-4.64 (m, 2 H), 6.91 (d, 1 H), 8.05 (s, 1 H), 8.18 (d, 1 H), 9.63 (s, 1 H), 12.18 (s, 1 H). LCMS m/z 454.

Workup

  1. customof two reaction vessels
  2. customEach vessel was irradiated in a CEM Discover microwave for 15 minutes at 150° C
  3. customthe resulting mixture irradiated for 15 minutes at 180° C
  4. customThe contents of the two reaction vessels
  5. stirringthe mixture was shaken again
  6. customThe layers were separated
  7. washThe organic layer was washed with water, hydrochloric acid (1M)
  8. additionwas added
  9. customthe layers were separated
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. temperatureThe pH of the aqueous layer was raised to about six
  14. additionby adding saturated sodium carbonate
  15. extractionthe aqueous layer was then extracted with ethyl acetate
  16. dry with materialThe organic layer was dried over magnesium sulfate
  17. filtrationfiltered
  18. additionadded to the above organic residue
  19. customevaporated
  20. customThe solution was purified by RP-HPLC on a Varian Dynamax C-18 column (250×41.4 mm) with a gradient of 10-95% acetonitrile/water (hydrochloric acid) over 15 minutes in two batches
  21. customevaporated

Sources & evidence

ORD record
ord-2c3008a5d14e44fb9ea73fd2b404b00e
Source dataset
uspto-grants-2013_08
Patent number
US08518956B2

Reaction notes

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