Sodium Carbonate → HCID 44232500, compound

HRID 1256295Notes

Reaction equation

HRID 1256295 reaction equation
[C:1]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]3[N:19]=[C:20]([CH3:22])[CH:21]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:25][CH2:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>N#N.[Cl-].[Na+].O.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]([C:5]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:31]3[CH:30]=[CH:29][CH:28]=[C:27]([CH2:26][OH:25])[CH:32]=3)[N:15]3[N:19]=[C:20]([CH3:22])[CH:21]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 866522574-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide2×

Product 1

HCID 44232500HCID 44232500, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 947NitrogenSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide (1K, 40 mg, 1.0 equivalent), 3-(hydroxymethyl)phenylboronic acid (1.9 equivalents), Pd(PPh3)4 (0.10 equivalent), and Na2CO3 (4.0 equivalents) in N2-saturated 5:1 DMF/H2O (0.05 M with respect to 1K) was stirred at 100° C. overnight. After cooling, the mixture was diluted with brine and extracted with EtOAc. Combined organic layers were dried over MgSO4, filtered and concentrated. The crude product was purified by chromatography (SiO2, gradient of 40 to 50% EtOAc/hexanes). The product was then recrystallized from CH2Cl2-hexanes to give the titled compound (62%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.37 (s, 9H) 2.50 (s, 3H) 4.83 (d, J=6.1 Hz, 2H) 6.29 (s, 1H) 7.44-7.71 (m, 5H) 7.88 (d, J=8.3 Hz, 2H) 8.03 (s, 1H) 8.15 (s, 1H) 8.59 (s, 1H).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc
  3. dry with materialCombined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (SiO2, gradient of 40 to 50% EtOAc/hexanes)
  7. customThe product was then recrystallized from CH2Cl2-hexanes

Sources & evidence

ORD record
ord-9ca34943cd494b5e9c83d0d4c62871a5
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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