Sodium Carbonate → 4-tert-butyl-N-(5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)benzamide

HRID 1924767Notes

Reaction equation

HRID 1924767 reaction equation
Br[C:2]1[N:7]=[C:6]2[S:8][C:9]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)=[N:10][C:5]2=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)O1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>O1CCOCC1.CN(C=O)C.N#N.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:12]([NH:11][C:9]2[S:8][C:6]3[C:5]([N:10]=2)=[CH:4][CH:3]=[C:2]([C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)[N:7]=3)=[O:23])=[CH:14][CH:15]=1)([CH3:22])([CH3:21])[CH3:20]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 58015373N-(5-bromothiazolo[5,4-b]pyridin-2-yl)-4-tert-butylbenzamide

Product 1

HCID 445467464-tert-butyl-N-(5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)benzamideYield 50%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 947NitrogenSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

The titled compound was prepared using a procedure analogous to that described in connection with 9 (Example 9). To a microwave vial, N-(5-bromothiazolo[5,4-b]pyridin-2-yl)-4-tert-butylbenzamide (4A, 120 mg, 1.0 equivalent) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.2 equivalent) in dioxane (0.17 M) and DMF (0.51 M) was stirred in N2. Followed by addition of Na2CO3 (2 M aqueous solution, 8.0 equivalents) and PdCl2(dppf)/DCM adduct (0.05 equivalent). The mixture was heated at 120° C. for 10 minutes. After cooling to room temperature, the crude mixture was added saturated aqueous NaHCO3 and extracted with EtOAc twice. Combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by chromatography (SiO2, gradient of 1 to 10% MeOH/CH2Cl2) to give the titled compound 10 (50%) as a tan solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33 (s, 9H) 7.61 (d, J=8.59 Hz, 2H) 8.08-8.16 (m, 4H) 8.27 (d, J=1.77 Hz, 2H) 8.72 (d, J=6.06 Hz, 2H) 13.07 (s, 1H); ESI-MS: m/z 389.0 (M+H)+.

Workup

  1. customThe titled compound was prepared
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with EtOAc twice
  4. dry with materialCombined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography (SiO2, gradient of 1 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4f85712386314b7b81af2f5603787dac
Source dataset
uspto-grants-2012_05
Patent number
US08178555B2

Reaction notes

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