1,4-Dioxane → tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 579321Notes

Reaction equation

HRID 579321 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]=2)=[N:4][N:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([N:37]2[CH:41]=[CH:40][CH:39]=[N:38]2)[CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>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.O>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([N:37]2[CH:41]=[CH:40][CH:39]=[N:38]2)[CH:25]=[CH:26][C:27]=1[C:2]1[S:6][C:5]([C:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]=2)=[N:4][N:3]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 867105591-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazoleHCID 86727142tert-butyl 4-(5-bromo-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 86727143tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 68.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a 5 mL microwave vial was added tert-butyl 4-(5-bromo-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (100 mg, 0.29 mmol), 1-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole (173 mg, 0.58 mmol), K3PO4 (153 mg, 0.72 mmol), and Pd(PPh3)4 (17 mg, 0.015 mmol), 1,4-dioxane (2 mL), and water (0.4 mL). The mixture was purged with N2 for 10 min and heated to 100° C. in the microwave for 1 hour. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Heptane) to give 87 mg (68.5%) of tert-butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate: MS (M+1)=440.4; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.57 (d, J=8.59 Hz, 1H), 8.03 (d, J=2.53 Hz, 1H), 7.78 (d, J=1.52 Hz, 1H), 7.62 (d, J=2.02 Hz, 1H), 7.32 (dd, J=2.02, 8.59 Hz, 1H), 6.59 (m, 1H), 6.51-6.55 (m, 1H), 4.15-4.22 (m, 2H), 4.11 (s, 3H), 3.69 (t, J=5.56 Hz, 2H), 2.78-2.90 (m, 2H), 1.51 (s, 9H).

Workup

  1. customThe mixture was purged with N2 for 10 min
  2. additionThe mixture was diluted with EtOAc
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (EtOAc/Heptane)

Sources & evidence

ORD record
ord-27209b1da9fa45b6a3906430c64d8dc3
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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