2-Bromopyridine → 1-(4-(Cyanomethyl)-1-(pyridin-2-yl)piperidin-4-yl)-3-(4-fluorophenylamino)-1H-pyrazole-4-carboxamide

HRID 521231노트

반응식

HRID 521231 반응식
FC(F)(F)C([O-])=O.[C:8]([C:11]1[C:12]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:13][N:14]([C:16]2([CH2:22][C:23]#[N:24])[CH2:21][CH2:20][NH2+:19][CH2:18][CH2:17]2)[CH:15]=1)(=[O:10])[NH2:9].[NH:33]1[CH2:40][CH2:39][CH2:38][C@H:34]1[C:35](O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].BrC1C=CC=CN=1>CS(C)=O.[Cu]I>[C:23]([CH2:22][C:16]1([N:14]2[CH:15]=[C:11]([C:8]([NH2:9])=[O:10])[C:12]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[N:13]2)[CH2:21][CH2:20][N:19]([C:40]2[CH:39]=[CH:38][CH:34]=[CH:35][N:33]=2)[CH2:18][CH2:17]1)#[N:24]

참가 물질

7

반응물 4

HCID 79732-BromopyridineHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 867294014-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate2회

생성물 1

HCID 867294021-(4-(Cyanomethyl)-1-(pyridin-2-yl)piperidin-4-yl)-3-(4-fluorophenylamino)-1H-pyrazole-4-carboxamide

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 679Dimethyl Sulfoxide용매

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온도
90 °C

실험 절차

A mixture of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (52 mg, 0.11 mmol), copper (I) iodide (2 mg, 0.01 mmol), L-proline (3 mg, 0.02 mmol) and K3PO4 (48 mg, 0.23 mmol) was dissolved in DMSO (0.16 mL). 2-Bromopyridine (0.011 mL, 0.11 mmol) was added, and the resulting mixture was heated to 90° C. and allowed to stir for 72 hours. The reaction mixture was then allowed to cool to ambient temperature and was filtered. The filtrate was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound as a solid.

후처리

  1. temperatureto cool to ambient temperature
  2. filtrationwas filtered
  3. customThe filtrate was purified by reverse-phase preparative HPLC (MeCN/water
  4. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-aa6957716229476fa59101d58f3ef884
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328099B2

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