Citric Acid → HCID 86687476, compound

HRID 1473431Notes

Reaction equation

HRID 1473431 reaction equation
F[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16]([S:22]([NH:25][C:26]1[CH:31]=[CH:30][N:29]=[CH:28][N:27]=1)(=[O:24])=[O:23])=[CH:17]2.[NH:32]1[CH:36]=[CH:35][N:34]=[CH:33]1.CC(C)([O-])C.[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1>[N:32]1([C:2]2[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[CH:4][C:3]=2[C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH:14]=[CH:15][C:16]([S:22]([NH:25][C:26]2[CH:31]=[CH:30][N:29]=[CH:28][N:27]=2)(=[O:23])=[O:24])=[CH:17]3)[CH:36]=[CH:35][N:34]=[CH:33]1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 795ImidazoleHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86687477HCID 86687477, compound

Product 1

HCID 86687476HCID 86687476, compoundYield 48.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

A microwave vial charged with 5-(2-fluoro-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide (0.111 g, 0.248 mmol), 1H-imidazole (0.051 g, 0.744 mmol), 1 mL dioxane, and lithium tert-butoxide (1N in THF) (0.992 ml, 0.992 mmol) was heated to 180° C. in the microwave for 90 minutes. LC/MS showed incomplete reaction, so the reaction mixture was heated to 180° C. for an additional 90 minutes. LC/MS showed mostly product, so the reaction mixture was poured into 1N citric acid solution and was extracted with EtOAc. The organics were concentrated. Purification of the crude residue by reverse phase column chromatography [10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(2-(1H-imidazol-1-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)naphthalene-2-sulfonamide (0.060 g, 0.121 mmol, 48.8% yield). 1H NMR (DMSO-d6) δ ppm: 8.57 (s, 1H), 8.54 (s, 1H), 8.20 (d, J=8.3 Hz, 1H), 7.95-8.04 (m, 2H), 7.70-7.80 (m, 2H), 7.62-7.68 (m, 1H), 7.56-7.62 (m, 1H), 7.53 (d, J=9.0 Hz, 1H), 7.48 (s, 1H), 6.98 (d, J=6.3 Hz, 1H), 6.94 (s, 1H), 6.60 (s, 1H). m/z (ESI) 496.0 (M+H)+

Workup

  1. customreaction
  2. temperatureso the reaction mixture was heated to 180° C. for an additional 90 minutes
  3. extractionwas extracted with EtOAc
  4. concentrationThe organics were concentrated
  5. customPurification of the crude residue by reverse phase column chromatography [10 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-defb6526e2714326ab31bb49c67d958a
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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