Dimethylformamide → HCID 117626358, compound

HRID 921073Notes

Reaction equation

HRID 921073 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1Cl)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].CC[N:30]([CH:34]([CH3:36])C)[CH:31]([CH3:33])C.[CH3:37][CH2:38][O:39][C:40]([CH3:42])=O.[CH3:43]N(C=O)C>CCOCC>[CH2:38]([O:39][C:40]1([CH3:42])[CH2:33][CH2:31][N:30]([C:17]2[N:16]3[N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=[C:15]3[N:14]=[C:13]([CH3:27])[C:12]=2[C@H:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:34][CH2:36]1)[CH:37]=[CH2:43]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 81531Diisopropylethylamine2×HCID 117626364HCID 117626364, compound

Product 1

HCID 117626358HCID 117626358, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (21.4 g, 53.8 mmol), 4-(allyloxy)-4-methylpiperidine, HCl (11.34 g, 59.2 mmol) and DIEA (10.33 ml, 59.2 mmol) in DMF (100 mL) was stirred at 60° C. (oil bath temp) for 22 h. Note: LCMS of the reaction mixture was identical at 2 and 22 h, indicating that there may not be enough amine for the reaction to complete. The amineHCl salt was free flowing liquid, possible due to the absorbtion of lot of water. So, additional amine HCl (7.85 g, 41 mmol) and DIEA (5 mL) were added and continued stirring at 60° C. for 4 h. Then, cooled, diluted with Et2O (300 mL), washed with water (3×50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated to give brown viscous oil. Flash chromatography using 4:1 Hex/EtOAc afforded (S)-ethyl 7-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (25.9 g, 50.1 mmol, 93% yield) as yellow paste. 1H NMR (400 MHz, CDCl3) δ 7.03 (s, 1H), 6.11-6.01 (m, 1H), 5.86 (br. s., 1H), 5.45 (d, J=17.8 Hz, 1H), 5.22 (dd, J=10.4, 1.6 Hz, 1H), 4.50-4.43 (m, 2H), 4.29-4.18 (m, 2H), 4.06-4.01 (m, 2H), 3.90-3.25 (br. s, 4H), 2.63 (s, 3H), 2.05-1.90 (m, 2H), 1.80-1.69 (m, 1H), 1.66-1.59 (m, 1H), 1.45 (t, J=7.1 Hz, 3H), 1.37 (s, 3H), 1.25-1.21 (m, 12H). LCMS (M+H)=517.5.

Workup

  1. customwas identical at 2 and 22 h
  2. customfor the reaction
  3. custompossible due to the absorbtion of lot of water
  4. stirringcontinued stirring at 60° C. for 4 h
  5. temperatureThen, cooled
  6. washwashed with water (3×50 mL), brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give brown viscous oil

Sources & evidence

ORD record
ord-696fd6ddba4e4c9899bb4c814bf8f15d
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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