Potassium Carbonate → HCID 86700301, compound

HRID 879486Notes

Reaction equation

HRID 879486 reaction equation
Br[C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([C@H:18]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:19]([O:21]CC)=[O:20])[C:8]([CH3:29])=[CH:7][C:5]=2[N:6]=1.C([O-])([O-])=O.[K+].[K+].[CH3:36][N:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=2)[C:39]([N:55]2[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]2)=[N:38]1.[OH-].[Na+]>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.CCO.O1CCOCC1.O>[C:25]([O:24][C@@H:18]([C:9]1[C:8]([CH3:29])=[CH:7][C:5]2[N:6]=[C:2]([C:43]3[CH:44]=[C:45]4[C:40]([C:39]([N:55]5[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]5)=[N:38][N:37]4[CH3:36])=[CH:41][CH:42]=3)[S:3][C:4]=2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:19]([OH:21])=[O:20])([CH3:28])([CH3:26])[CH3:27]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 86700302HCID 86700302, compound

Product 1

HCID 86700301HCID 86700301, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (75 mg, 0.151 mmol), KHCO3 (15.2 mg, 0.151 mmol), K2CO3 (41.7 mg, 0.302 mmol), 1-methyl-3-(4-methylpiperazin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (55 mg, 0.154 mmol), Pd(PPh3)4 (17 mg, 15 μmol), H2O (400 μL), and dioxane (1.6 mL). The vessel was sealed and heated to 100° C. for 2 h. Then EtOH (absolute, 800 μL) and 2 M aq NaOH (400 μL) were added. Heating was continued at 100° C. for 3 h. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C33H36ClN5O3S: 618.2, 620.2 (M+H+); Found: 618.3, 620.2 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.10 (s, 1H), 7.93-7.83 (m, 2H), 7.79-7.65 (m, 2H), 7.64-7.55 (m, 3H), 5.16 (s, 2H), 4.09 (d, J=12.9 Hz, 1H), 3.97 (s, 3H), 3.63 (d, J=8.7 Hz, 2H), 3.39 (d, J=11.5 Hz, 2H), 3.36-3.22 (m, 2H), 3.00 (s, 3H), 2.62 (s, 3H), 0.98 (s, 9H).

Workup

  1. customThe vessel was sealed
  2. temperatureHeating
  3. temperatureThe reaction was cooled to 23° C.
  4. filtrationfiltered
  5. filtration(0.45 micron teflon syringe filter)
  6. customThe filtrate was purified by reverse phase HPLC
  7. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-599f562bd5644173bff3c7c86133230f
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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