Triethylamine → HCID 66793278, compound

HRID 1254435Notes

Reaction equation

Br[C:2]1[C:3]([F:17])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.C(N(CC)CC)C.[CH2:25]([OH:29])[CH2:26][C:27]#[CH:28]>CCOC(C)=O.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.[Cu]I>[F:17][C:3]1[C:2]([C:28]#[C:27][CH2:26][CH2:25][OH:29])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][N:7]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 5-bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (2.80 g, 9.36 mmol, Intermediate 18), Pd(PPh3)2Cl2 (660 mg, 0.94 mmol), CuI (180 mg, 0.94 mmol), and triethylamine (50 mL) was added but-3-yn-1-ol (2.0 g, 28.1 mmol) under N2 atmosphere. The resulting mixture was stirred at 60° C. for 16 hours. Upon completion, the reaction mixture was diluted with EtOAc, and washed with water (3×10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified on silica gel column (0˜20% EtOAc in petroleum ether) affording the title compound (2.0 g). 1H NMR (300 MHz, DMSO-d6): δ 8.33 (s, 1H), 7.64 (d, 1H), 7.49 (dd, 1H), 5.94 (dd, 1H), 4.99 (t, 1H), 3.98-3.92 (m, 1H), 3.85-3.77 (m, 1H), 3.68 (t, 2H), 2.67 (t, 2H), 2.48-2.35 (m, 1H), 2.12-2.02 (m, 2H), 1.84-1.78 (m, 1H), 1.68-1.62 (m, 2H).

Workup

washwashed with water (3×10 mL)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified on silica gel column (0˜20% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-fcc40a8987e24ef58a7acf8ad4f07867
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455534B2

Reaction notes

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