Potassium Carbonate → HCID 44124934, compound

HRID 1692016Notes

Reaction equation

HRID 1692016 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:31]1[N:36]=[C:35]([C:37]([O:39][CH3:40])=[O:38])[CH:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+]>C(O)(C)(C)C.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([C:31]5[N:36]=[C:35]([C:37]([O:39][CH3:40])=[O:38])[CH:34]=[CH:33][CH:32]=5)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 16217886Methyl 6-bromopyridine-2-carboxylateHCID 66905591HCID 66905591, compound

Product 1

HCID 44124934HCID 44124934, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

A vial containing (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (Example 64A, 30 mg, 0.072 mmol), methyl 6-bromo-2-pyridinecarboxylate (16 mg, 0.072 mmol), K2CO3 (30 mg, 0.22 mmol) and bis(triphenylphosphine)palladium(II) chloride (5 mg, 7 μmol) in tert-butanol (0.5 mL) was heated to 80° C. for 1 hour and cooled. The mixture was diluted with CH2Cl2 (5 mL), filtered, and concentrated. The residue was purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm) as described in Example 65. The title compound was obtained as the bis trifluoroacetate salt. 1H NMR (300 MHz, CD3OD) δ ppm 1.52-1.65 (m, 1H), 1.74-1.93 (m, 3H), 1.96-2.09 (m, 2H), 2.34-2.48 (m, 1H), 2.63-2.76 (m, 1H), 3.04-3.20 (m, 2H), 3.52-3.77 (m, 3H), 3.81-3.95 (m, 2H), 4.01 (s, 3H), 4.08-4.21 (m, 2H), 7.64 (d, J=8.5 Hz, 1H), 7.98-8.07 (m, 2H), 8.08-8.15 (m, 2H), 8.57 (d, J=1.7 Hz, 1H); MS (DCI/NH3) m/z 423 (M+H)+.

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm)

Sources & evidence

ORD record
ord-91a711fe487b44629e52e9ba9f16956f
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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