Triphenylphosphine → 5-[(4-Fluorophenyl)carbonyl]-2-[(2-methylpyridin-4-yl)methoxy]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine

HRID 571733

Reaction equation

HRID 571733 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:36][C:37]1[CH:42]=[C:41]([CH2:43][OH:44])[CH:40]=[CH:39][N:38]=1.[F:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]([N:54]2[CH2:59][CH2:58][N:57]3[N:60]=[C:61](O)[CH:62]=[C:56]3[CH2:55]2)=[O:53])=[CH:48][CH:47]=1>C1COCC1>[F:45][C:46]1[CH:47]=[CH:48][C:49]([C:52]([N:54]2[CH2:59][CH2:58][N:57]3[N:60]=[C:61]([O:44][CH2:43][C:41]4[CH:40]=[CH:39][N:38]=[C:37]([CH3:36])[CH:42]=4)[CH:62]=[C:56]3[CH2:55]2)=[O:53])=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 9942144(2-Methylpyridin-4-yl)methanolHCID 178519627HCID 178519627, compound

Product 1

HCID 727032155-[(4-Fluorophenyl)carbonyl]-2-[(2-methylpyridin-4-yl)methoxy]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazineYield 35.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

Di-tert-butyl azodicarboxylate (0.138 g, 0.6 mmol) was added to a stirred solution of triphenylphosphine (0.157 g, 0.6 mmol), (2-methylpyridin-4-yl)methanol (0.074 g, 0.6 mmol) and 5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ol (0.157 g, 0.6 mmol) in THF (3 mL) in a sealed tube and under nitrogen. The mixture was stirred at 130° C. for 20 minutes under microwave irradiation and the solvents were evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7 M solution of ammonia in methanol in DCM 0/100 to 5/95, twice). The desired fractions were collected, the solvents evaporated in vacuo and the residue triturated with DIPE to yield 5-[(4-fluorophenyl)carbonyl]-2-[(2-methylpyridin-4-yl)methoxy]-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (0.078 g, 35% yield) as a white solid. C20H19FN4O2. 1H NMR (400 MHz, CDCl3) δ ppm 2.56 (s, 3 H), 4.08 (br. s., 4 H), 4.74 (br. s., 2 H), 5.17 (s, 2 H), 5.52 (br. s., 1 H), 7.10-7.18 (m, 3 H), 7.21 (br. s, 1 H), 7.45-7.52 (m, 2 H), 8.47 (d, J=5.1 Hz, 1 H).

Workup

  1. customthe solvents were evaporated in vacuo
  2. customThe crude product was purified by flash column chromatography (silica
  3. customThe desired fractions were collected
  4. customthe solvents evaporated in vacuo
  5. customthe residue triturated with DIPE

Sources & evidence

ORD record
ord-48b4d776c259422cb876f6f6b47b7b98
Source dataset
uspto-grants-2015_05
Patent number
US09029366B2

Linked notes

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