Potassium Carbonate → (2S)-2-tert-butoxy-2-(5-methyl-2-(3-(1-methyl-1H-indazol-5-yl)phenyl)-7-(2-methylbenzo[d][1,3]dioxol-5-yl)benzo[d]thiazol-6-yl)ethyl pivalate

HRID 510307Notes

Reaction equation

HRID 510307 reaction equation
[C:1]([O:7][CH2:8][C@H:9]([C:15]1[C:39]([CH3:40])=[CH:38][C:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]4[CH:29]=[C:30]5[C:34](=[CH:35][CH:36]=4)[N:33]([CH3:37])[N:32]=[CH:31]5)[CH:23]=3)[S:21][C:17]=2[C:16]=1Br)[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].CC1(C)C(C)(C)OB([C:50]2[CH:59]=[CH:58][C:53]3[O:54][CH:55]([CH3:57])[O:56][C:52]=3[CH:51]=2)O1.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>[C:1]([O:7][CH2:8][C@@H:9]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:15]1[C:39]([CH3:40])=[CH:38][C:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]4[CH:29]=[C:30]5[C:34](=[CH:35][CH:36]=4)[N:33]([CH3:37])[N:32]=[CH:31]5)[CH:23]=3)[S:21][C:17]=2[C:16]=1[C:50]1[CH:59]=[CH:58][C:53]2[O:54][CH:55]([CH3:57])[O:56][C:52]=2[CH:51]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 86699810(S)-2-(7-bromo-5-methyl-2-(3-(1-methyl-1H-indazol-5-yl)phenyl)benzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalateHCID 866998384,4,5,5-Tetramethyl-2-(2-methylbenzo[d][1,3]dioxol-5-yl)-1,3,2-dioxaborolane

Product 1

HCID 86699837(2S)-2-tert-butoxy-2-(5-methyl-2-(3-(1-methyl-1H-indazol-5-yl)phenyl)-7-(2-methylbenzo[d][1,3]dioxol-5-yl)benzo[d]thiazol-6-yl)ethyl pivalate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (S)-2-(7-bromo-5-methyl-2-(3-(1-methyl-1H-indazol-5-yl)phenyl)benzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate (16 mg, 0.025 mmol) and 4,4,5,5-tetramethyl-2-(2-methylbenzo[d][1,3]dioxol-5-yl)-1,3,2-dioxaborolane (13 mg, 0.050 mmol) in 1,4-dioxane was added Pd(PPh3)4 (4 mg, 3.1×10−3 mmol) and 2M K2CO3 (66 μL, 0.133 mmol). The reaction was degassed for 5 minutes with N2 and then heated to 110° C. for 1 h. After cooling, the reaction mixture was diluted with EtOAc, extracted with saturated NaHCO3, brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 0 to 10% ethyl acetate/hexanes) to give the product. LCMS-ESI+ (m/z): [M+H]+ calcd for C41H44N3O5S: 690.30; found: 690.4.

Workup

  1. customThe reaction was degassed for 5 minutes with N2
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. extractionextracted with saturated NaHCO3, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 0 to 10% ethyl acetate/hexanes)
  9. customto give the product

Sources & evidence

ORD record
ord-f3f9ce9ee84948fa8bc9db3b2df6fc23
Source dataset
uspto-grants-2015_08
Patent number
US09096586B2

Reaction notes

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