Sodium Carbonate → HCID 90389218, compound

HRID 2203410Notes

Reaction equation

HRID 2203410 reaction equation
[C:1]([O:5][C:6]([N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15](Br)[CH:16]=2)[N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([OH:43])=[C:38](B(O)O)[CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.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:5][C:6]([N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:36]3[CH:35]=[C:34]([Cl:33])[CH:39]=[CH:38][C:37]=3[OH:43])[CH:16]=2)[N:11]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 23005362(5-Chloro-2-hydroxyphenyl)boronic Acid (contains varying amounts of Anhydride)HCID 66820624HCID 66820624, compound

Product 1

HCID 90389218HCID 90389218, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of tert-butyl 3-[bis(tert-butoxycarbonyl)amino]-5-bromo-1H-indazole-1-carboxylate (2.97 g, 5.81 mmol) in dimethoxyethane (25 mL) was added (5-chloro-2-hydroxyphenyl)boronic acid (1.00 g, 5.81 mmol), tetrakis(triphenylphosphine)palladium (0.67 g, 0.58 mmol) and 2 M aqueous sodium carbonate (5.8 mL, 11.6 mmol). The mixture was heated at refluxed for 5 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was diluted with ethyl acetate (50 mL), washed with water (2×20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 30-60% gradient of ethyl acetate in hexanes to afford tert-butyl 3-[bis(tert-butoxycarbonyl)amino]-5-(5-chloro-2-hydroxyphenyl)-1H-indazole-1-carboxylate as a colorless solid in 84% yield (2.57 g): 1H NMR (300 MHz, DMSO-d6) δ8.21 (d, J=7.8 Hz, 1H), 7.62-7.59 (m, 2H), 7.46 (s, 1H), 6.90-6.86 (m, 2H), 5.33 (br s, 1H), 1.72 (s, 9H), 1.42 (s, 18H); MS (ES+) m/z 560.0 (M+1), 562.0 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat refluxed for 5 h
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with ethyl acetate (50 mL)
  5. washwashed with water (2×20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography
  10. washeluting with a 30-60% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d5ba6483ed4544b19d038799db88a660
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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