Diisopropylethylamine → HCID 178440458, compound

HRID 1931598Notes

Reaction equation

HRID 1931598 reaction equation
C(O[C:6]([NH:8][NH:9][C@H:10]1[CH2:15][CH2:14][C@@H:13]([C:16]2[O:20][N:19]=[C:18]([CH:21]([CH3:23])[CH3:22])[N:17]=2)[CH2:12][CH2:11]1)=O)(C)(C)C.[Cl:24][C:25]1[C:30](C=O)=[C:29](Cl)[N:28]=[CH:27][N:26]=1.C(N(C(C)C)CC)(C)C>O1CCCC1>[Cl:24][C:25]1[N:26]=[CH:27][N:28]=[C:29]2[N:9]([C@H:10]3[CH2:11][CH2:12][C@@H:13]([C:16]4[O:20][N:19]=[C:18]([CH:21]([CH3:22])[CH3:23])[N:17]=4)[CH2:14][CH2:15]3)[N:8]=[CH:6][C:30]=12

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 8196914,6-Dichloro-5-pyrimidinecarbaldehyde2×HCID 178440462HCID 178440462, compound2×

Product 1

HCID 178440458HCID 178440458, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N′-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cis-cyclohexyl]-hydrazinecarboxylic acid tert-butyl ester (Intermediate 13; 309 mg, 2.03 mmol) in tetrahydrofuran (3 mL) was added to a cooled (0° C.) solution of 4,6-dichloro-pyrimidine-5-carbaldehyde (Intermediate 16; 169 mg, 0.95 mmol) and diisopropylethylamine (337 μL, 1.9 mmol) in tetrahydrofuran (2 mL), and the mixture was stirred at 0° C. for 30 min and then at room temperature for 5 h. The mixture was filtered, and the filtrate was washed with brine. The aqueous layer was extracted with methyl tert-butyl ether and the organic extracts were combined, washed with brine, dried (sodium sulfate), filtered, evaporated, and held under high vacuum. Toluene (10 mL) was added and the mixture was held at 110° C. overnight. The solvent was evaporated and the residue was purified on a Supelco 23 g column, eluting with 0-3% methanol/dichloromethane to give 4-chloro-1-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cis-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidine (211 mg, 64%).

Workup

  1. waitat room temperature for 5 h
  2. filtrationThe mixture was filtered
  3. washthe filtrate was washed with brine
  4. extractionThe aqueous layer was extracted with methyl tert-butyl ether
  5. washwashed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. additionToluene (10 mL) was added
  10. waitthe mixture was held at 110° C. overnight
  11. customThe solvent was evaporated
  12. customthe residue was purified on a Supelco 23 g column
  13. washeluting with 0-3% methanol/dichloromethane

Sources & evidence

ORD record
ord-bc955283b7ef45479a22cd1c5bb78450
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…