Triphenylphosphine → 6-cyclobutyl-5-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,3-triazolo[1,5-alpha]pyrimidine

HRID 1250180Notes

Reaction equation

HRID 1250180 reaction equation
[CH:1]1([C:5]2[C:6](=[O:21])[NH:7][C:8]3[N:9]([N:11]=[N:12][C:13]=3[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[CH:10]=2)[CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:41]([N:43]1[C:47]([CH2:48]O)=[N:46][CH:45]=[N:44]1)[CH3:42].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH:1]1([C:5]2[C:6]([O:21][CH2:48][C:47]3[N:43]([CH2:41][CH3:42])[N:44]=[CH:45][N:46]=3)=[N:7][C:8]3[N:9]([N:11]=[N:12][C:13]=3[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[CH:10]=2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 11412385(1-ethyl-1H-1,2,4-triazol-5-yl)methanolHCID 178518574HCID 178518574, compound

Product 1

HCID 538342426-cyclobutyl-5-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,3-triazolo[1,5-alpha]pyrimidineYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-Cyclobutyl-3-(2-fluorophenyl)-4H-1,2,3-triazolo[1,5-α]pyrimidin-5-one (50 g, 0.18 mmol), triphenylphosphine (120 mg, 0.44 mmol) and (2-ethyl-2H-1,2,4-triazol-3-yl)methanol (60 mg, 0.44 mmol) were suspended in dry tetrahydrofuran (1.5 ml). Diethyl azodicarboxylate (70 μl, 0.44 mmol) was added and a solution resulted immediately. The reaction was stirred at room temperature for 48 hours before purification by preparative tlc (60% EtOAc/hexanes) to afford a colourless oil which crystallised upon the addition of diethyl ether. The white solid was collected by filtration and stirred in diethyl ether for 6 hours and collected by filtration to afford 6-cyclobutyl-5-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,3-triazolo[1,5-α]pyrimidine (41 mg; 59%) as white needles, m.p. 188-191° C.; δH (360 MHz, CDCl3) 1.42 (3H, t, J=7.3 Hz, NCH2CH3), 1.89-1.94 (1H, m, CH(CH2)3), 2.04-2.15 (3H, m, CH(CH2)3), 2.36-2.43 (2H, m, CH(CH2)3), 4.25 (2H, q, J=7.3 Hz, NCH2CH3), 5.65 (2H, s, OCH2), 7.19-7.31 (2H, m, ArH), 7.36-7.42 (1H, m, ArH), 7.92 (1H, s, triazole CH), 7.99 (1H, td, J=7.5 and 1.7 Hz, ArH), 8.59 (1H, d, J=1 Hz, pyrimidine CH); m/z (ES+) 394 (M+H+).

Workup

  1. customa solution resulted immediately
  2. customto afford a colourless oil which
  3. customcrystallised upon the addition of diethyl ether
  4. filtrationThe white solid was collected by filtration
  5. filtrationcollected by filtration

Sources & evidence

ORD record
ord-6e5c61e639634877a08a83d607a3b4ad
Source dataset
uspto-grants-2002_01
Patent number
US06337331B1

Reaction notes

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