Sodium Carbonate → HCID 178518682, compound

HRID 2358268Notes

Reaction equation

HRID 2358268 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:35][C:12]2=[C:13]3[C:18](=[C:19]4[CH:24]=[C:23](B5OC(C)(C)C(C)(C)O5)[CH:22]=[CH:21][C:20]4=[C:11]2[N:10]=1)[C:17](=[O:34])[NH:16][CH:15]=[CH:14]3.Br[C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]([C:23]2[CH:22]=[CH:21][C:20]3=[C:11]4[N:10]=[C:9]([C:3]5[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=5[F:1])[NH:35][C:12]4=[C:13]4[C:18]([C:17](=[O:34])[NH:16][CH:15]=[CH:14]4)=[C:19]3[CH:24]=2)=[N:38][CH:39]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 8170982-Bromo-5-chloropyridineHCID 178431009HCID 178431009, compound

Product 1

HCID 178518682HCID 178518682, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a pressure flask with stir bar, the intermediate from Example 10 Step A (75mg, 0.16 mmol), 2-bromo-5-chloropyridine (33.5 mg, 0.17 mmol), and (Ph3P)2PdCl2 (11.1 mg, 0.02 mmol) were added. The flask was purged of air and back-filled with argon (3×). Toluene (0.79 ml) and ethanol (0.79 ml) were bubbled with argon for at least 10 min before addition to the flask. Na2CO3 (0.24 ml, 0.48 mmol) was bubbled with argon, and then added to the flask. The mixture was heated at 90° C. in an oil bath overnight. Water was added to quench the reaction. The water layer was extracted with ethyl acetate 3×. The combined organics were washed with brine, dried with MgSO4, filtered, and concentrated in vacuo. The crude compound was purified by reverse phase HPLC (10-100% acetonitrile in H2O+0.05% TFA) to afford a light yellow solid. 1H NMR (600 MHz, CD3OD) δ 14.00 (m, 1H), 11.40 (m, 1H), 10.97 (s, 1H), 8.73 (s, 1H); 8.53 (d, 1H); 8.29 (s, 1H); 8.05 (s, 2H); 7.56 (m, 3H); 7.25 (d, 2H): [M+H]+ 459.

Workup

  1. customThe flask was purged of air
  2. additionback-filled with argon (3×)
  3. customToluene (0.79 ml) and ethanol (0.79 ml) were bubbled with argon for at least 10 min before addition to the flask
  4. additionadded to the flask
  5. customto quench
  6. customthe reaction
  7. extractionThe water layer was extracted with ethyl acetate 3×
  8. washThe combined organics were washed with brine
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude compound was purified by reverse phase HPLC (10-100% acetonitrile in H2O+0.05% TFA)
  13. customto afford a light yellow solid

Sources & evidence

ORD record
ord-1c8280f66feb4cd5859fb82d4bf4dc4a
Source dataset
uspto-grants-2010_07
Patent number
US07763634B2

Reaction notes

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