Potassium Carbonate → HCID 118144944, compound

HRID 523959Notes

Reaction equation

HRID 523959 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][C:18]3[O:19][C:20]([F:23])([F:22])[O:21][C:17]=3[CH:16]=2)(=[O:13])=[O:12])=[CH:7][C:6]=1[F:35])([CH3:4])([CH3:3])[CH3:2].C[O:37][C:38]([C:40]1[CH:41]=[CH:42][C:43](Br)=[C:44]2[C:49]=1[N:48]=[CH:47][CH:46]=[CH:45]2)=[O:39].C([O-])([O-])=O.[K+].[K+].O[Li].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:25]([C:43]3[CH:42]=[CH:41][C:40]([C:38]([OH:39])=[O:37])=[C:49]4[C:44]=3[CH:45]=[CH:46][CH:47]=[N:48]4)=[CH:24][C:18]3[O:19][C:20]([F:22])([F:23])[O:21][C:17]=3[CH:16]=2)(=[O:12])=[O:13])=[CH:7][C:6]=1[F:35])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 168937Lithium hydroxide, monohydrateHCID 71607288Methyl 5-bromoquinoline-8-carboxylateHCID 123497520HCID 123497520, compound

Product 1

HCID 118144944HCID 118144944, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of the 4-tert-butyl-N-[2,2-difluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzodioxol-5-yl]-3-fluorobenzenesulfonamide (3.2 g, 6.22 mmol), methyl-5-bromoquinoline-8-carboxylate (Example 1, step-b, 1.66 g, 6.22 mmol) and 2 M aq. K2CO3 (7.8 mL, 15.55 mmol) in 1,4-dioxane (50 mL) was purged with nitrogen for 5 minutes. Pd(PPh3)4 (360 mg, 0.31 mmol, 5 mol %) was added and the reaction mixture was heated at 95° C. for overnight. The reaction mixture was cooled to r.t. LiOH.H2O (2.6 g, 62.2 mmol) was added and heated at 80° C. for 1 hour. Cooled to r.t, pH of the reaction medium was adjusted to ˜6 with 2N aq.HCl, extracted with ethyl acetate, dried (Na2SO4), filtered and concentrated. The residue was triturated with methanol to get pure (>95%) title compound as an off-white solid (1.75 g, 50%). 1H NMR (400 MHz, CD3OD) δ 8.96-8.94 (m, 1H), 8.57 (d, J=7.4 Hz, 1H), 7.93-7.91 (m, 1H), 7.57-7.54 (m, 2H), 7.42-(t, J=7.8 Hz, 1H), 7.30-7.26 (m, 1H), 7.18-7.15 (m, 1H), 7.05 (d, J=7.5 Hz, 1H), 6.88 (s, 1H), 6.56 (br, 1H), 1.43 (s, 9H); MS: (ES) m/z calculated for C27H21F3N2O6S.

Workup

  1. customwas purged with nitrogen for 5 minutes
  2. temperatureThe reaction mixture was cooled to r.t
  3. temperatureheated at 80° C. for 1 hour
  4. temperatureCooled
  5. extractionHCl, extracted with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-11e2b8b8127b401e9e36b41b987d85af
Source dataset
uspto-grants-2016_05
Patent number
US09340509B2

Reaction notes

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