Acetyl chloride → 1-(4-(4-((1-(Quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-5-yl)piperidin-1-yl)ethanone

HRID 454948Notes

Reaction equation

HRID 454948 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:9]([O:14][CH:15]3[CH2:18][N:17]([C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[CH2:16]3)=[N:10][CH:11]=[N:12][CH:13]=2)[CH2:4][CH2:3]1.CCN(CC)CC.[C:36](Cl)(=[O:38])[CH3:37].O.CC#N>C(Cl)Cl>[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[CH:28][C:19]=1[N:17]1[CH2:16][CH:15]([O:14][C:9]2[C:8]([CH:5]3[CH2:6][CH2:7][N:2]([C:36](=[O:38])[CH3:37])[CH2:3][CH2:4]3)=[CH:13][N:12]=[CH:11][N:10]=2)[CH2:18]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 18373917Acetonitrile--water (1/1)HCID 674774162-(3-((5-(Piperidin-4-yl)pyrimidin-4-yl)oxy)azetidin-1-yl)quinoline hydrochloride

Product 1

HCID 546709551-(4-(4-((1-(Quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-5-yl)piperidin-1-yl)ethanoneYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(3-((5-(piperidin-4-yl)pyrimidin-4-yl)oxy)azetidin-1-yl)quinoline hydrochloride in CH2Cl2 (10 mL) were added Et3N (100 mg, 0.99 mmol) and acetyl chloride (62 mg, 0.79 mmol). The reaction mixture was stirred at room temperature for 1 hour, then diluted with CH2Cl2 (20 mL), washed with water (20 mL). The organic layer was washed with brine (20 mL), dried over Na2SO4, and filtered, evaporated to give the crude product. Purified by column chromatography, and followed by prep. HPLC (10% to 80% water/MeCN) to give 1-(4-(4-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyrimidin-5-yl)piperidin-1-yl)ethanone (34 mg, 0.08 mmol, yield 13%). M+1 IC50 (uM) 404 0.765 1H NMR (CDCl3, 400 MHz) δ (ppm) 8.73 (s, 1H), 8.44 (s, 1H), 8.14 (d, J=9.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.75-7.65 (m, 2H), 7.47-7.40 (m, 1H), 6.64 (d, J=9.2 Hz, 1H), 5.71 (s, 1H), 5.04-4.98 (m, 2H), 4.79-4.71 (m, 2H), 4.68-4.63 (m, 1H), 3.97-3.93 (m, 1H), 3.26-3.19 (m, 1H), 3.11-3.04 (m, 1H), 2.71-2.64 (m, 1H), 2.14 (s, 3H), 2.03-1.89 (m, 2H), 1.69-1.63 (m, 2H).

Workup

  1. washwashed with water (20 mL)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give the crude product
  7. customPurified by column chromatography

Sources & evidence

ORD record
ord-f7daa51a28cb4db69d0ba3f167dc6f53
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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