2,2,2-Trifluoroethylamine hydrochloride → HCID 71526224, compound

HRID 1477810Notes

Reaction equation

HRID 1477810 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([NH:14][C@@H:15]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:16](O)=[O:17])=[O:13])[CH:9]=[N:8][C:7]=2[N:23]2[CH2:26][C:25]([F:28])([F:27])[CH2:24]2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[F:61][C:62]([F:66])([F:65])[CH2:63][NH2:64]>CN(C=O)C>[CH3:22][CH:20]([CH3:21])[CH2:19][C@H:15]([NH:14][C:12]([C:10]1[CH:9]=[N:8][C:7]([N:23]2[CH2:26][C:25]([F:27])([F:28])[CH2:24]2)=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[N:11]=1)=[O:13])[C:16](=[O:17])[NH:64][CH2:63][C:62]([F:66])([F:65])[F:61]

Participants

6

Reactant 4

HCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 86682339HCID 86682339, compound

Product 1

HCID 71526224HCID 71526224, compoundYield 75.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-{[6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyrazine-2-carbonyl]-amino}-4-methyl-pentanoic acid (40 mg, 100 μmol) was suspended in DMF (2 mL). TBTU (35.5 mg, 110 μmol), DIEA (85.9 μl, 0.5 mmol) and 2,2,2-trifluoro-ethanamine hydrochloride (1:1) (CAN 373-88-6, 15 mg, 135 μmol) were added and the reaction mixture was stirred at room temperature for 16 hours. The mixture was concentrated in vacuo; ethyl acetate (3 mL) and 2N NaOH solution (2 mL) were added before eluting with ethyl acetate through ChemElut (10 g). The filtrate was concentrated in vacuo and purified by flash chromatography (silica gel, 10 g, 0% to 100% ethyl acetate in n-heptane) to give the desired product (36 mg, 75%) as white solid; LC-MS (UV peak area, ESI) 100%, 480.2035 (M+H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionethyl acetate (3 mL) and 2N NaOH solution (2 mL) were added
  3. washbefore eluting with ethyl acetate through ChemElut (10 g)
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by flash chromatography (silica gel, 10 g, 0% to 100% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-6ecc572f364543659676b4ad29209cb5
Source dataset
uspto-grants-2016_08
Patent number
US09403808B2

Reaction notes

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