Diisopropylethylamine → 2-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)thiazol-2-yloxy)pyridine

HRID 1893716Notes

Reaction equation

HRID 1893716 reaction equation
Br[C:2]1[N:3]=[C:4]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[S:5][CH:6]=1.[CH3:14][O:15][C:16]1[CH:36]=[CH:35][C:19]([CH2:20][N:21]2[CH:25]=[C:24](B3OC(C)(C)C(C)(C)O3)[CH:23]=[N:22]2)=[CH:18][CH:17]=1.C(N(C(C)C)C(C)C)C>O1CCOCC1.O.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]>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:20][N:21]2[CH:25]=[C:24]([C:2]3[N:3]=[C:4]([O:7][C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=4)[S:5][CH:6]=3)[CH:23]=[N:22]2)=[CH:35][CH:36]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 534402131-(4-methoxybenzyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 668718162-(4-Bromothiazol-2-yloxy)pyridine

Product 1

HCID 668891372-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)thiazol-2-yloxy)pyridineYield 14.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

According to Scheme 3, Step 3: A mixture of 2-(4-bromothiazol-2-yloxy)pyridine (1.56 mmol, 400 mg), 1-(4-methoxybenzyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.87 mmol, 587 mg), PdCl2(dppf) (0.16 mmol, 127 mg) and N-ethyl-N-isopropylpropan-2-amine (3.11 mmol, 0.53 mL) in dioxane/water (1:1, 10 mL) was stirred at 150° C. for 1 hour under microwave conditions. The reaction mixture was filtered through a pad of celite and was washed with DCM. The organic phase was washed with water, was dried over MgSO4, was filtered and was concentrated under reduced pressure. The crude mixture was purified by flash chromatography over silica gel using cyclohexane/EtOAc (90:10 to 70:30) as eluent to yield 2-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)thiazol-2-yloxy)pyridine (0.23 mmol, 83 mg, 9%) as an oil.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of celite
  2. washwas washed with DCM
  3. washThe organic phase was washed with water
  4. dry with materialwas dried over MgSO4
  5. filtrationwas filtered
  6. concentrationwas concentrated under reduced pressure
  7. customThe crude mixture was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-9aa6d61415754e028475a30de29149ec
Source dataset
uspto-grants-2013_08
Patent number
US08513252B2

Reaction notes

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