Piperidine → 4-[1-(2-aminopyrimidin-4-yl)-1H-1,3-benzodiazol-6-yl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol

HRID 1398505Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:6]=2[CH:17]=1.N1CCCCC1.[S:24]1[CH:28]=[CH:27][N:26]=[C:25]1[C:29]([OH:33])([C:31]#[CH:32])[CH3:30]>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.[Cu]I>[NH2:16][C:12]1[N:11]=[C:10]([N:7]2[C:6]3[CH:17]=[C:2]([C:32]#[C:31][C:29]([C:25]4[S:24][CH:28]=[CH:27][N:26]=4)([OH:33])[CH3:30])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH:15]=[CH:14][N:13]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a pressure tube was added 4-(6-bromo-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (70% purity, 790 mg, 1.91 mmol), followed by piperidine (4 mL), tetrakis(triphenylphosphine)palladium (220 mg, 0.19 mmol), copper(I) iodide (36.3 mg, 0.19 mmol)) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (584.04 mg, 3.81 mmol). The reaction was capped and stirred at 75° C. for 3.5 hr. The reaction mixture was concentrated in vacuo and purified by flash chromatography (Isolute column, 2% MeOH in DCM to 3% MeOH in DCM) followed by reverse phase preparative HPLC to give the title compound as a pale yellow solid: 1H NMR (500 MHz, DMSO) δ 1.92 (3H, s), 7.03 (1H, br. s.), 7.08-7.20 (3H, m), 7.38 (1H, dd, J=8.35, 1.58 Hz), 7.69 (1H, d, J=3.15 Hz), 7.74 (1H, d, J=8.35 Hz), 7.78 (1H, d, J=3.31 Hz), 8.38 (1H, d, J=5.52 Hz), 8.56 (1H, d, J=0.95 Hz), 9.08 (1H, s); LC-MS: m/z=+363.4 (M+H)+.

Workup

customThe reaction was capped
concentrationThe reaction mixture was concentrated in vacuo
custompurified by flash chromatography (Isolute column, 2% MeOH in DCM to 3% MeOH in DCM)

Sources & evidence

ORD record: ord-0f50ab12fbdb4958b38418e9eef8b22e
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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