Triethylamine → N2-(4-bromo-5-methylisoxazol-3-yl)-N1-(cyanomethyl)leucinamide

HRID 1744108Notes

Reaction equation

HRID 1744108 reaction equation
[Br:1][C:2]1[C:3]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[N:4][O:5][C:6]=1[CH3:7].Cl.[NH2:18][CH2:19][C:20]#[N:21].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[C:3]([NH:8][C@H:9]([C:14]([NH:21][CH2:20][C:19]#[N:18])=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13])=[N:4][O:5][C:6]=1[CH3:7]

Participants

6

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 11491918Aminoacetonitrile hydrochlorideHCID 69153233N-(4-bromo-5-methylisoxazol-3-yl)leucine

Product 1

HCID 86594565N2-(4-bromo-5-methylisoxazol-3-yl)-N1-(cyanomethyl)leucinamide

Procedure

To N-(4-bromo-5-methylisoxazol-3-yl)leucine (841 mg, 2.90 mmol), aminoacetonitrile hydrochloride (674 mg, 7.30 mmol), PyBOP (1.73 g, 3.33 mmol) in dry degassed DMF (60 mL) was added triethylamine (1.4 mL, 10.0 mmol) dropwise. The reaction mixture was stirred for 15 hours at room temperature. Aqueous sat. NaHCO3 was added and the product was extracted with diethyl ether (2×) and ethyl acetate (2×). The combined organic extracts were washed with brine, dried over sodium sulphate, and concentrated in vacuo. The crude product was purified by flash chromatography (60% ethyl acetate/hexane) to yield N2-(4-bromo-5-methylisoxazol-3-yl)-N1-(cyanomethyl)leucinamide.

Workup

  1. customdegassed DMF (60 mL)
  2. extractionthe product was extracted with diethyl ether (2×) and ethyl acetate (2×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4a40aaed6cd84b60b9da905d20c52a8b
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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