Water → HCID 86677528, compound

HRID 1497885Notes

Reaction equation

HRID 1497885 reaction equation
[F:1][C:2]1([F:9])[CH2:5][CH:4]([C:6]([OH:8])=O)[CH2:3]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=1[F:33])[C:26](=[NH:29])[NH:27]O.O>CN1C(=O)CCC1>[F:9][C:2]1([F:1])[CH2:3][CH:4]([C:6]2[O:8][N:29]=[C:26]([C:25]3[CH:30]=[CH:31][C:32]([F:33])=[C:23]([CH:24]=3)[NH2:22])[N:27]=2)[CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 137777893,3-Difluorocyclobutane-1-carboxylic acidHCID 178513325HCID 178513325, compound

Product 1

HCID 86677528HCID 86677528, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3,3-difluorocyclobutanecarboxylic acid (0.90 g, 6.6 mmol) in NMP (5 mL) was slowly added CDI (1.07 g, 6.6 mmol). The resulting mixture was stirred at room temperature for 30 minutes. Then 3-amino-4-fluoro-N-hydroxybenzimidamide (87) (0.56 g, 3.3 mmol) was added and stirred for another 30 minutes until LCMS indicated complete reaction. The mixture was then heated at 125° C. for 15 minutes in a microwave reactor and poured into water (100 mL). The mixture was extracted with EtOAc (2×50 mL), dried over Na2SO4, filtered and concentrated to give a crude product which was purified by silica-gel chromatography (0-60% EtOAc in hexanes) to afford 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-fluoroaniline (88). 1H NMR (400 MHz, CDCl3) δ 7.53 (dd, J=2.0, 8.4 Hz, 1H), 7.43-7.48 (m, 1H), 7.10 (dd, J=10.8, 8.4 Hz, 1H), 3.90 (br, 2H), 3.67 (m, 1H), 3.09-3.18 (m, 4H). MS m/z 270.1 (M+1)+.

Workup

  1. stirringstirred for another 30 minutes until LCMS
  2. customreaction
  3. temperatureThe mixture was then heated at 125° C. for 15 minutes in a microwave reactor
  4. extractionThe mixture was extracted with EtOAc (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product which
  9. customwas purified by silica-gel chromatography (0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c1fb9da489b54e15b3a4dbf7d2d53bb3
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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