Hydrochloric Acid → HCID 22050338, compound

HRID 1866974Notes

Reaction equation

HRID 1866974 reaction equation
[Cl:1][C:2]1[C:3](=[O:28])[N:4]([C:18]2[C:25](F)=[CH:24][C:21]([C:22]#[N:23])=[CH:20][C:19]=2[F:27])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[K].Cl.[O:31]1CCCC1>O>[Cl:1][C:2]1[C:3](=[O:28])[N:4]([C:18]2[C:25]([OH:31])=[CH:24][C:21]([C:22]#[N:23])=[CH:20][C:19]=2[F:27])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 5462222PotassiumHCID 22050211HCID 22050211, compound

Product 1

HCID 22050338HCID 22050338, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-1(2H)-yl]-3,5-difluorobenzonitrile (522 mg, 1.28 mmol) and potassium trimethylsilonate 90% (655 mg, 4.60 mmol) are combined in 8 ml anhydrous tetrahydrofuran and stirred under nitrogen at room temperature for 2 hours. The precipitated potassium salt of was collected by filtration, washed with a minimum of tetrahydrofuran, and dried in vacuo. A portion of this salt (275 mg, 0.618 mmol) was dissolved in 5 ml water, the pH was adjusted below 6 with concentrated hydrochloric acid, the product collected by filtration, washed with water, sucked dry under a blanket of dry nitrogen, and dried further in vacuo overnight (251 mg, 100%, 98% overall). 1H-NMR (400 MHz, DMSO-d6) δ 11.46 (br s, 1H), 7.74 (d, J=7.81 Hz, 1H), 7.67 (quartet, J=6.76 Hz, 1H), 7.52 (d, J=8.76, 1H), 7.364, (dt, J=10.18, 2.37 Hz, 1H), 7.24 (br s, 1H), 7.17 (br t, J=8.75, 1H), 6.74 (d, J=8.04 Hz, 1H), 5.39 (s, 2H). 19F-NMR (400 MHz, DMSO-d6) δ −109.26 (quintet, J=8.50 Hz, 1F), −113.52 (quartet, J=9.29 Hz, 1F), −118.06 (d, J=9.38 Hz, 1F). LC/MS tr=5.13 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes, then 95% acetonitrile for 2 minutes, at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 407 (M+H). ES-HRMS m/z 407.0381 (M+H calcd for C19H11ClF3N2O3 requires 407.0405).

Workup

  1. filtrationThe precipitated potassium salt of was collected by filtration
  2. washwashed with a minimum of tetrahydrofuran
  3. customdried in vacuo
  4. filtrationthe product collected by filtration
  5. washwashed with water
  6. customsucked dry under a blanket of dry nitrogen
  7. customdried further in vacuo overnight (251 mg, 100%, 98% overall)
  8. waitLC/MS tr=5.13 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes
  9. wait95% acetonitrile for 2 minutes
  10. customat 50° C.

Sources & evidence

ORD record
ord-205201992f0643bf90a87e56ec90ca71
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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