Acetonitrile → HCID 71523334, compound

HRID 1621020Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[O:13]1[CH2:17][CH2:16][CH:15]([C:18]2([CH:22]=[O:23])[CH2:21][CH2:20][CH2:19]2)[CH2:14]1.CC#N>C1COCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH:22]([C:18]1([CH:15]2[CH2:16][CH2:17][O:13][CH2:14]2)[CH2:19][CH2:20][CH2:21]1)[OH:23]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-bromopyridine (203 mg, 1.28 mmol) in THF (5 mL) was added 2.5N n-BuLi solution (0.6 mL, 1.54 mmol) dropwise and stirred at −78° C. for 1.5 hours. Then a solution of Example 284C (0.18 g, 1.17 mmol) in THF (2 mL) was added and stirred at room temperature for 1 hour. The reaction mixture was quenched with aqueous NH4Cl solution and extracted with EtOAc (2×20 mL). The combined organic phase was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by Prep-HPLC(C18 column, water (0.05% TFA):CH3CN, 55:45 to 85:15) to obtain the title compound as a colorless oil (31.2 mg, yield 11.5%). LC-MS: MS (M+H)+ 234.1; 1H NMR (400 MHz, CDCl3): δ 8.55 (d, J=4.8 Hz, 1H), 7.69-7.64 (m, 1H), 7.30 (d, J=7.6 Hz 1H), 7.26-7.22 (m, 1H), 4.71 (d, J=28.8 Hz, 1H), 4.53 (brs, 1H), 3.89-3.79 (m, 1.5H), 3.65-3.54 (m, 2H), 3.38 (t, J=8.6 Hz, 0.5H), 2.35-2.04 (m, 3H), 1.99-1.55 (m, 6H).

Workup

stirringstirred at room temperature for 1 hour
customThe reaction mixture was quenched with aqueous NH4Cl solution
extractionextracted with EtOAc (2×20 mL)
washThe combined organic phase was washed with brine (10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by Prep-HPLC(C18 column, water (0.05% TFA)

Sources & evidence

ORD record: ord-a1a1526b5ee14471a57fc71512158c95
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772500B2

Reaction notes

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