Chloroacetyl chloride → HCID 68565012, compound

HRID 572309Notes

Reaction equation

HRID 572309 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([C:11]2[S:12][C:13]([C:16]3[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=3)=[CH:14][CH:15]=2)=[O:10])[CH2:4]1.C(N(CC)CC)C.[Cl:33][CH2:34][C:35](Cl)=[O:36]>C1COCC1>[Cl:33][CH2:34][C:35]([NH:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([C:11]2[S:12][C:13]([C:16]3[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=3)=[CH:14][CH:15]=2)=[O:10])[CH2:4]1)=[O:36]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 131729820HCID 131729820, compound

Product 1

HCID 68565012HCID 68565012, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ((S)-3-Amino-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochloride (Example 26, 79 mg, 0.20 mmol) and triethylamine (69 μL, 0.42 mmol) in THF (3 mL) was treated with chloroacetyl chloride (18 μL, 0.22 mmol), stirred for 1 hr and evaporated to a solid. The solid was triturated and filtered with the aid of water, then air dried to provide the 2-Chloro-N-{(S)-1-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carbonyl]-piperidin-3-yl}-acetamide intermediate as a colorless solid (75 mg, 86%). LC/MS 6.13 min, [M+1]+ 436. The chloroacetyl intermediate (35 mg, 0.08 mmol) was dissolved in acetonitrile (3 mL) containing anhydrous K2CO3, treated with morpholine (14 μL, 0.16 mmol), and stirred for 3 days. The reaction mixture was then evaporated and treated with water to provide an oil which was then triturated with water (3×2 mL), dissolved in EtOAc (4 mL), dried over MgSO4, filtered, and evaporated to afford product as an oil (34 mg, 87%). 1H NMR (CDCl3) 1.62-1.76 (m, 3H), 1.88-1.98 (m, 1H), 2.29 (d, J=1.3, 3H), 2.45-2.48 (m, 4H), 2.93 (s, 2 H), 3.52 (br s, 1H), 3.63-3.67 (m, 4H), 3.72-3.92 (m, 2H), 3.98-4.08 (m, 1H), 7.32 (br s, 1 H), 7.41 (s, 2H). 19F NMR −63.1. LC/MS 4.68 min, [M+1]+487.

Workup

  1. customevaporated to a solid
  2. customThe solid was triturated
  3. filtrationfiltered with the aid of water
  4. customair dried

Sources & evidence

ORD record
ord-f2a01207b04b4bb3a00a75067a2618b4
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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