Potassium Carbonate → HCID 86700292, compound

HRID 879477Notes

Reaction equation

HRID 879477 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.[CH3:30][N:31]1[C:39]2[C:34](=[CH:35][C:36](B(O)O)=[CH:37][CH:38]=2)[C:33]([CH3:43])=[N:32]1.C([O-])([O-])=O.[K+].[K+].[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>[C:25]([O:24][C@@H:18]([C:9]1[C:8]([CH3:29])=[CH:7][C:5]2[N:6]=[C:2]([C:36]3[CH:35]=[C:34]4[C:39](=[CH:38][CH:37]=3)[N:31]([CH3:30])[N:32]=[C:33]4[CH3:43])[S:3][C:4]=2[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=1)[C:19]([OH:21])=[O:20])([CH3:26])([CH3:28])[CH3:27]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 441194901,3-DiMethylindazole-5-boronic acidHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700292HCID 86700292, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 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 (100 mg, 0.202 mmol), 1,3-dimethylindazole-5-boronic acid (42 mg, 0.22 mmol), Pd(PPh3)4 (23 mg, 20 μmol), 2 M aq K2CO3 (800 μL), and dioxane (3.2 mL). The reaction was heated to 100° C. for 2 h. The reaction was treated with absolute EtOH (1.6 mL) and 10 M aq NaOH (800 μL). After heating to 100° C. for 2 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 C29H28ClN3O3S: 534.2, 536.2 (M+H+). Found: 534.3, 536.3 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.35 (s, 1H), 8.08 (dd, J=8.9, 1.6 Hz, 1H), 7.81 (s, 1H), 7.75-7.64 (m, 1H), 7.62-7.52 (m, 4H), 5.26 (s, 1H), 4.01 (s, 3H), 2.61 (s, 3H), 2.57 (s, 3H), 0.98 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-d3a05a7323eb425692c5a95c2d1042ce
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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