N,1-dimethylpyrrolidin-3-amine → HCID 178423457, 화합물

HRID 77109

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HRID 77109 반응식
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]2)=[CH:5][C:4]=1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=2[N:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:52][NH:53][CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1>>[CH3:52][N:53]([CH:54]1[CH2:58][CH2:57][N:56]([CH3:59])[CH2:55]1)[C:15]([CH:12]1[CH2:11][CH2:10][N:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([C:18]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([CH3:27])=[CH:26][C:20]=4[N:19]=3)[CH:5]=2)[CH2:14][CH2:13]1)=[O:17]

참가 물질

4

반응물 3

HCID 2758520N,1-dimethylpyrrolidin-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178423459HCID 178423459, 화합물

생성물 1

HCID 178423457HCID 178423457, 화합물수율 37%

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온도
35 °C

실험 절차

Method Q—Step a To a mixture of 1-[4-chloro-3-(5-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid hydrochloride (obtained as described in general method 3,4, step e) (0.01 g, 0.25 mmol) in dcm (2 mL), HATU (0.10 g, 0.26 mmol), TEA (0.07 mL, 0.53 mmol) and methyl-(1-methyl-pyrrolidin-3-yl)-amine (0.03 g, 0.31 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature, washed with ammonium chloride solution (2 mL), filtered through a phase separator and organic phase was filtered by SCX column (eluent: first dcm:MeOH/1:1 then NH3 in MeOH (2N)). This work up was done using the Zinsser Speedy (version 6.1.3). The crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1) to obtain 0.04 g of the title compound (37%). 1H-NMR (400 MHz, CD3OD): δ 1.76-1.93 (5H, m), 2.08-2.23 (2H, m), 2.36-2.48 (6H, m), 2.51-3.09 (9H, m), 3.83-3.86 (2H, m), 5.13-5.20 (1H, m), 7.09-7.13 (2H, m), 7.38-7.40 (3H, m), 7.51 (1H, bs); m/z 466 (M+H)+, retention time (method b)=2.30 (10 min run)

후처리

  1. additionwere added
  2. temperaturecooled to room temperature
  3. washwashed with ammonium chloride solution (2 mL)
  4. filtrationfiltered through a phase separator and organic phase
  5. filtrationwas filtered by SCX column (eluent
  6. customThe crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1)

출처 및 근거

ORD 기록
ord-d383427c471749b58667f644ea369eb4
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835648B2

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