Trifluoroacetic acid → HCID 86687669, compound

HRID 1473605Notes

Reaction equation

HRID 1473605 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:30]1[S:31][CH:32]=[CH:33][N:34]=1)[S:7]([C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[C:16]([C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22]([NH2:24])=O)=[N:15][CH:14]=[C:13]2[F:29])(=[O:9])=[O:8].O=P(Cl)(Cl)Cl.C(O)(C(F)(F)F)=O>N1C=CC=CC=1.C(OCC)(=O)C>[C:22]([C:21]1[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=1[C:16]1[C:17]2[C:12](=[CH:11][C:10]([S:7]([NH:6][C:30]3[S:31][CH:32]=[CH:33][N:34]=3)(=[O:8])=[O:9])=[CH:19][CH:18]=2)[C:13]([F:29])=[CH:14][N:15]=1)#[N:24]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 24813Phosphorus oxychlorideHCID 86687668HCID 86687668, compound

Product 1

HCID 86687669HCID 86687669, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-(6-(N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)-4-fluoroisoquinolin-1-yl)benzamide was dissolved in pyridine (0.6 mL) and cooled to 0° C. POCl3 (0.023 mL, 0.243 mmol) was added. The reaction was stirred for 5 minutes at room temperature. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated and purified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM) to afford 1-(2-cyanophenyl)-4-fluoro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.02 (br. s., 1H), 8.84 (d, J=1.6 Hz, 1H), 8.57 (d, J=1.3 Hz, 1H), 8.13-8.03 (m, 2H), 7.99-7.86 (m, 2H), 7.83-7.73 (m, 2H), 7.68-7.51 (m, 2H), 7.31 (d, J=4.5 Hz, 1H), 6.90 (d, J=4.6 Hz, 1H). m/z (ESI) 410.9 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe material was dissolved in DCM
  7. stirringThe reaction was stirred for 30 minutes at room temperature
  8. concentrationThe reaction was concentrated
  9. custompurified via column chromatography (RediSep Gold 12 g, gradient elution 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-f9f03b59bcb649968164928e550087bc
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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