Ethyl 4-piperidinecarboxylate → Ethyl 1-(6-methylpyridazin-3-yl)piperidine-4-carboxylate

HRID 4946

반응식

HRID 4946 반응식
[CH3:1][C:2]1[N:7]=[N:6][C:5](Cl)=[CH:4][CH:3]=1.[NH:9]1[CH2:19][CH2:18][CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:10]1>CN1C(=O)CCC1.C(N(C(C)C)CC)(C)C>[C:13]([CH:12]1[CH2:11][CH2:10][N:9]([C:5]2[N:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH2:19][CH2:18]1)([O:15][CH2:16][CH3:17])=[O:14]

참가 물질

5

반응물 2

HCID 70770Ethyl 4-piperidinecarboxylateHCID 2272543-Chloro-6-methylpyridazine

생성물 1

HCID 19797305Ethyl 1-(6-methylpyridazin-3-yl)piperidine-4-carboxylate수율 44%

시약·촉매·용매 2

HCID 13387N-methyl-2-pyrrolidone용매HCID 81531Diisopropylethylamine용매

실험 절차

55 mmoles of 6-methyl-3-chloropyridazine was added to 75 mmoles of ethyl isonipecotate in 5 mL NMP and 20 mL diisopropylethylamine (DIPEA) and refluxed for 6 hours. The product was isolated as described in Example 1a above to give a 44% yield of 3-(4-carboethoxy-1-piperidinyl)-6-methylpyridazine. Reduction of 18.8 mmol of this compound using 56.6 mmol DIBAL in 100 mL THF with a Rochelle's salt quench gave 3-(4-hydroxymethyl-1-piperidinyl)-6-methylpyridazine (Formula IV: R1 =CH3 ; Y=CH2) which was used unpurified in the final step. Reaction of 5 mmol of the product described in Example 1b with 4.5 mmol of the 3-(4-hydroxymethyl-1-piperidinyl)-6-methyl pyridazine according to the procedure of Example 1c afforded after recrystallization from ethyl acetate at -70° C. the compound of formula I (R1 =R4 =CH3, Y=CH 2, R2 =R3 =hydrogen) in 12% yield, m.p. 180°-185° C.

후처리

  1. temperaturerefluxed for 6 hours
  2. customThe product was isolated

출처 및 근거

ORD 기록
ord-3c595b8a98d54bcaa7886c6e9630ad8a
출처 데이터셋
uspto-grants-1993_09
특허 번호
US05242924

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