Diisopropylethylamine → HCID 178440459, compound

HRID 1931599Notes

Reaction equation

HRID 1931599 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 178440459HCID 178440459, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N′-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-trans-cyclohexyl]-hydrazinecarboxylic acid tert-butyl ester (Intermediate 13; 691 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; 361 mg, 2.03 mmol) and diisopropylethylamine (718 μL, 4.06 mmol) in anhydrous tetrahydrofuran (6 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 (15 mL) was added and the mixture was held at 110° C. overnight. The solvent was evaporated and the residue was purified on a Supelco 50 g column, eluting with 0-3% methanol/dichloromethane to give 4-chloro-1-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-trans-cyclo-hexyl]-1H-pyrazolo[3,4-d]pyrimidine (489 mg, 69%). 1H NMR (300 MHz, DMSO-d6) δ 1.24 (d, 6H, J=6.9 Hz), 1.74-1.88 (m, 2H), 2.04-2.28 (m, 6H), 2.98-3.08 (m, 1H), 3.11-3.22 (m, 1H), 4.91-4.97 (m, 1H), 8.49 (s, 1H), 8.86 (s, 1H).

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 (15 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 50 g column
  13. washeluting with 0-3% methanol/dichloromethane

Sources & evidence

ORD record
ord-f88280e3f67d49ed90805a632d11a995
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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