4-(Bromomethyl)benzoic acid → 5-Bromo-3-(5-(4-(bromomethyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine

HRID 331513Notes

Reaction equation

HRID 331513 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][NH2:12])=[O:10])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.[Br:13][CH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](O)=O)=[CH:17][CH:16]=1.BrP(Br)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>C(#N)C>[Br:8][C:5]1[N:4]=[C:3]([C:9]2[O:10][C:19]([C:18]3[CH:22]=[CH:23][C:15]([CH2:14][Br:13])=[CH:16][CH:17]=3)=[N:12][N:11]=2)[C:2]([NH2:1])=[N:7][CH:6]=1

Participants

6

Reactant 4

HCID 225994-(Bromomethyl)benzoic acidHCID 70579Triphenylphosphine dibromideHCID 81531DiisopropylethylamineHCID 580702563-Amino-6-bromopyrazine-2-carbohydrazide

Product 1

HCID 580704675-Bromo-3-(5-(4-(bromomethyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amineYield 77.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 1 L 3 neck round bottom flask was fitted with a mechanical stirrer, a cooling bath used as secondary containment, an addition funnel, a J-Kem temperature probe and a nitrogen inlet/outlet. The vessel was charged under nitrogen with 3-amino-6-bromopyrazine-2-carbohydrazide (12 g, 51.72 mmol), 4-(bromomethyl)benzoic acid (11.12 g, 51.72 mmol) and acetonitrile (460 ml, 20 ml/g based on the mass of the two reagents). Stirring was commenced and the pot temperature was recorded at 21° C. The suspension was then treated with dibromo(triphenyl)phosphorane (98.22 g, 232.7 mmol) added as a solid in one portion. The suspension was continued to stir at ambient temperature for 1 hour. The addition funnel was then charged with diisopropylethylamine (54 ml, 310.3 mmol) which was added neat drop wise over 1 hour, which resulted in an exotherm to 30° C. The resulting light brown suspension was continued to stir at ambient temperature for 20 hours. The reaction mixture was vacuum filtered through a glass frit buchner funnel and the filter cake was displacement washed with acetonitrile (2×150 ml) followed by hexane (250 ml). The material was further dried under vacuum to provide the product 5-bromo-3-(5-(4-(bromomethyl)phenyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine as a yellow solid (16.4 g, 39.89 mmol, 77% yield). 1H NMR (400.0 MHz, DMSO-d6) δ 4.82 (s, 2H), 7.72 (d, J=8.2 Hz, 2H), 7.80 (s, 2H), 8.11 (d, J=8.1 Hz, 2H), 8.45 (s, 1H)

Workup

  1. customwas recorded at 21° C
  2. additionadded as a solid in one portion
  3. stirringto stir at ambient temperature for 1 hour
  4. additionwas added neat drop wise over 1 hour
  5. customwhich resulted in an exotherm to 30° C
  6. stirringto stir at ambient temperature for 20 hours
  7. filtrationfiltered through a glass frit buchner funnel
  8. washwashed with acetonitrile (2×150 ml)
  9. customThe material was further dried under vacuum

Sources & evidence

ORD record
ord-80d0aebded134716aa8600d4a9b13b0f
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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