Potassium Carbonate → (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(pyridin-4-yl)-1H-indazol-5-yl)benzo[d]thiazol-6-yl)acetate

HRID 879418Notes

Reaction equation

HRID 879418 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:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:19]([O:21][CH3:22])=[O:20])[C:8]([CH3:28])=[CH:7][C:5]=2[N:6]=1.[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:37]=2)[C:32]([C:48]2[CH:53]=[CH:52][N:51]=[CH:50][CH:49]=2)=[N:31]1.C([O-])([O-])=O.[K+].[K+].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.O>[C:24]([O:23][C@@H:18]([C:9]1[C:8]([CH3:28])=[CH:7][C:5]2[N:6]=[C:2]([C:35]3[CH:34]=[C:33]4[C:38](=[CH:37][CH:36]=3)[N:30]([CH3:29])[N:31]=[C:32]4[C:48]3[CH:53]=[CH:52][N:51]=[CH:50][CH:49]=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]([O:21][CH3:22])=[O:20])([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 86699809Methyl (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetateHCID 867002231-methyl-3-(pyridin-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole

Product 1

HCID 86700222(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(pyridin-4-yl)-1H-indazol-5-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a vial flushed with argon was added (S)-methyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (100 mg, 0.207 mmol), 1-methyl-3-(pyridin-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (53 mg, 0.16 mmol), Pd(PPh3)4 (18 mg, 16 μmol), and K2CO3 (66 mg, 0.47 mmol). De-gassed dioxane (2 mL) and water (0.5 mL) were then added, and the reaction was heated to 100° C. for 1 h. After cooling to 23° C., the reaction was filtered over a plug of Celite, concentrated, and purified by column chromatography (gradient 0 to 75% EtOAc in hexanes) to give the product. 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J=5.9 Hz, 2H), 8.64 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.94 (d, J=5.9 Hz, 2H), 7.89 (s, 1H), 7.61-7.39 (m, 5H), 5.21 (s, 1H), 4.18 (s, 3H), 3.75 (s, 3H), 2.60 (s, 3H), 0.99 (s, 9H).

Workup

  1. customTo a vial flushed with argon
  2. temperatureAfter cooling to 23° C.
  3. filtrationthe reaction was filtered over a plug of Celite
  4. concentrationconcentrated
  5. custompurified by column chromatography (gradient 0 to 75% EtOAc in hexanes)
  6. customto give the product

Sources & evidence

ORD record
ord-e38b21ae64c84843ad2cc49958f60c7b
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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