Potassium Carbonate → tert-Butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1429525Notes

Reaction equation

HRID 1429525 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][N:13]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][CH2:23][CH3:24])=[CH:18][N:17]=4)[CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[CH2:22]([C:19]1[CH:18]=[N:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([O:9][C:7]3[S:8][C:4]4[CH:3]=[C:2]([C:35]5[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=5)[CH:26]=[CH:25][C:5]=4[N:6]=3)[CH2:11][CH2:12]2)=[N:21][CH:20]=1)[CH2:23][CH3:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 674627936-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole

Product 1

HCID 67464591tert-Butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 6-bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole (190 mg, 0.438 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (163 mg, 0.526 mmol) and K2CO3 (182 mg, 1.315 mmol) in dioxane (3 mL) and water (1 mL) was added Pd(Ph3P)4 (25.3 mg, 0.022 mmol). Upon completion of addition, the reaction mixture was heated to 100° C., where it stirred overnight. At the conclusion of this period, the reaction mixture was cooled to rt, diluted with water and then extracted with CH2Cl2 (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to afford Compound 1D as a white solid (166 mg, 0.310 mmol, 71% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 8.17 (2H, s), 7.62-7.65 (1H, m), 7.62 (1H, s), 7.40 (1H, dd, J=8.5, 1.9 Hz), 6.00-6.09 (1H, m), 5.42-5.49 (1H, m), 4.23 (2H, ddd, J=13.3, 6.7, 3.9 Hz), 4.05-4.13 (2H, m), 3.63-3.76 (4H, m), 2.53-2.61 (2H, m), 2.41 (2H, t, J=7.6 Hz), 2.14-2.23 (2H, m), 1.95 (2H, dddd, J=12.8, 8.5, 8.4, 3.9 Hz), 1.57-1.64 (2H, m), 1.51 (9H, s), 0.95 (3H, t, J=7.3 Hz).

Workup

  1. additionUpon completion of addition
  2. temperatureAt the conclusion of this period, the reaction mixture was cooled to rt
  3. extractionextracted with CH2Cl2 (3×10 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue
  8. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-42629acb2866459d86a846ef2be5b1e6
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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