Diisopropylethylamine → HCID 117843068, compound

HRID 2209222Notes

Reaction equation

HRID 2209222 reaction equation
C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([C:31]2[N:32]=[C:33]([O:41][C@@H:42]([C@H:44]3[CH2:48][NH:47][C:46](=[O:49])[CH2:45]3)[CH3:43])[C:34]3[N:35]([N:37]=[CH:38][C:39]=3[CH3:40])[CH:36]=2)[CH:22]=[CH:23][C:24]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.[O:50]1[CH2:53][C:52](=O)[CH2:51]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(OCC)(=O)C>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([C:31]2[N:32]=[C:33]([O:41][C@@H:42]([C@H:44]3[CH2:48][NH:47][C:46](=[O:49])[CH2:45]3)[CH3:43])[C:34]3[N:35]([N:37]=[CH:38][C:39]=3[CH3:40])[CH:36]=2)[CH:22]=[CH:23][C:24]=1[N:25]1[CH2:26][CH2:27][N:28]([CH:52]2[CH2:53][O:50][CH2:51]2)[CH2:29][CH2:30]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 117843751HCID 117843751, compound

Product 1

HCID 117843068HCID 117843068, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

N,N-diisopropylethylamine (0.02 mL, 0.09 mmol) was added to a mixture of (R)-4-((R)-1-(6-(3-methoxy-4-(piperazin-1-yl)phenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one 2,2,2-trifluoroacetate 5.60 (21.45 mg, 0.04 mmol) in THF (1.5 mL) at room temperature. 3-Oxetanone (0.03 mL, 0.39 mmol) was added, followed by sodium triacetoxyborohydride (58 mg, 0.27 mmol) and mixture was heated at 50° C. After 3 hours, mixture was cooled to room temperature, diluted with 20 mL ethyl acetate, and washed with 8 mL water/10 mL sat Na2CO3(aq). Layers were separated and aqueous layer was extracted with ethyl acetate. Combined organics were dried, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (0-12% MeOH/CH2Cl2) to yield (R)-4-((R)-1-((6-(3-methoxy-4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one 5.63 (9 mg).

Workup

  1. temperaturemixture was cooled to room temperature
  2. washwashed with 8 mL water/10 mL
  3. customLayers were separated
  4. extractionaqueous layer was extracted with ethyl acetate
  5. customCombined organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (0-12% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ac2c577bb81241c7a8f5b8cfe7bb2669
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

Loading…