Dimethylformamide → Cyclopropanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amide

HRID 449027Notes

Reaction equation

HRID 449027 reaction equation
[Cl:1][C:2]1[C:3]([CH:8]([NH2:22])[C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[CH:23]1([C:26](O)=[O:27])[CH2:25][CH2:24]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN(C=O)C>>[Cl:1][C:2]1[C:3]([CH:8]([NH:22][C:26]([CH:23]2[CH2:25][CH2:24]2)=[O:27])[C:9]2[CH:10]=[CH:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59341168HCID 59341168, compound

Product 1

HCID 86636029Cyclopropanecarboxylic acid [(3-chloropyrazin-2-yl)-(4-phenoxyphenyl)-methyl]-amideYield 120.4%

Procedure

In a 10 mL flask were added C-(3-chloropyrazin-2-yl)-C-(4-phenoxyphenyl)-methylamine (110 mg, 0.00035 mol), cyclopropanecarboxylic acid (0.056 mL, 0.00070 mol), DIEA (0.55 mL, 0.0032 mol), TBTU (0.17 g, 0.00053 mol) and DMF (5 mL, 0.07 mol). The reaction mixture was stirred at rt for 10 min. Reaction was left to stir over weekend. The reaction mixture was concentrated in vacuo, dissolved in DCM and washed with sat aq NaHCO3 followed by brine. The organics were collected and concentrated in vacuo to give 160 mg of the compound as a yellow solid. Purification by prep TLC in 60% EtOAc: hexanes afforded 55 mg of the title compound as a yellow solid. The compound was carried on to the next step. MS (ES+): m/z 380.08 (20)[MH+]. HPLC: tR=3.56 min (Open lynx polar—5 min).

Workup

  1. customReaction
  2. waitwas left
  3. stirringto stir over weekend
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. dissolutiondissolved in DCM
  6. washwashed with sat aq NaHCO3
  7. customThe organics were collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ed1b348b8f0449a1a19842a04e73d88d
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

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