Triethylamine → HCID 69371692, compound

HRID 724429Notes

Reaction equation

HRID 724429 reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6](/[CH:19]=[CH:20]/[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.[C:27](=[O:30])([O-])[O-].[K+].[K+].C([N:35]([CH2:38][CH3:39])CC)C.[C:40]([O:43][CH2:44][CH3:45])(=[O:42])C.[CH3:46][CH2:47][CH2:48][CH2:49]CC>C1(OC)C=CC=CC=1.C([O-])(O)=O.[Na+].C(OCC)(=O)C.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>[CH3:14][Si:15]([CH3:17])([CH3:16])[CH2:45][CH2:44][O:43][C:40](=[O:42])[NH:35][C:38]1[CH:39]=[CH:49][CH:48]=[C:47]([C:27]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)=[N:7][N:8]3[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)=[O:30])[CH:46]=1

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 21226206Ethyl acetate hexaneHCID 21877280HCID 21877280, compound

Product 1

HCID 69371692HCID 69371692, compoundYield 79%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 7519AnisoleSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-iodo-3-((E)-2-pyridin-2-yl-vinyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole (7.1 g, 14.8 mmol), (3-boronic acid-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester (8.32 g, 29.6 mmol), dichlorobis(triphenylphosphine)-palladium(II) (312 mg, 0.44 mmol), potassium carbonate (6.13 g, 44.4 mmol) and triethylamine (2.1 ml, 14.8) in anisole (60 ml) was heated to 80° C. under an atmosphere of carbon monoxide. After 24 h more triethylamine (2.1 ml, 14.8 mmol) was added. After 33 hrs the reaction was determined to be complete by TLC analysis (ethyl acetate-hexane 7–3). The reaction mixture was cooled to 23° C., then diluted with saturated NaHCO3 (aq) (40 ml) and ethyl acetate (300 ml). The phases were separated and the aqueous was extracted with ethyl acetate (2×100 mls). The pooled ethyl acetate was washed with brine (100 ml) and dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography gave (3-{1-[3-(2-Pyridin-2-yl-ethyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-6-yl]-methanoyl}-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester as a yellow glass (7.22 g, 79%). 1H NMR (300 MHz, CDCl3) δ 8.65 (d, 1H, J=3.93 Hz), 8.10 (d, 1H, J=8.54 Hz), 8.04 (s, 1H), 7.94 (d, 1H, J=16.33 Hz), 7.82 (s, 1H), 7.66–7.77 (m, 3H), 7.61 (d, 1H, J=16.35 Hz), 7.40–7.51 (m, 3H), 7.19 (m, 1H), 7.00 (s, 1H), 5.77 (s, 2H), 4.25 (t, 2H, J=6.93 Hz), 3.60 (t, 2H, J=8.10 Hz), 1.04 (t, 2H, J=6.79 Hz), 1.00 (t, 2H, J=8.13 Hz), 0.04 (s, 9H), 0.0 (s, 9H). MS (ESI+) [M+H]/z Calc'd 615. found 615.

Workup

  1. temperatureThe reaction mixture was cooled to 23° C.
  2. customThe phases were separated
  3. extractionthe aqueous was extracted with ethyl acetate (2×100 mls)
  4. washThe pooled ethyl acetate was washed with brine (100 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-b1b01f5a61964153b67010dc727d2137
Source dataset
uspto-grants-2006_11
Patent number
US07141587B2

Reaction notes

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