Sodium Carbonate → HCID 68516875, compound

HRID 2241341Notes

Reaction equation

HRID 2241341 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.CC1(C)C(C)(C)OB([C:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH:38]=2)O1.C([O-])([O-])=O.[Na+].[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.COCCOC>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:16]2[CH:15]=[CH:14][N:13]=[C:12]3[N:8]([CH2:7][C:6]4[CH:27]=[CH:28][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[N:9]=[C:10]([C:37]4[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH:38]=4)[C:11]=23)=[C:19]([F:25])[CH:20]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 68516875HCID 68516875, compoundYield 98.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (250.0 mg, 0.5099 mmol, prepared in Example 7, step B), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (315.3 mg, 1.020 mmol), tetrakis(triphenylphosphine)palladium (117.8 mg, 0.1020 mmol), 1M Na2CO3 (1.275 ml, 2.550 mmol) and DME (25 mL). The reaction mixture was stirred at 100° C. overnight. The reaction was cooled to room temperature and partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (273.3 mg, 98%). LRMS (APCI pos): >99% purity, 254 nm, m/e 546 (M+1).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude material was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-5937b177bc4b409dbcc9d1d538f60df5
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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