Diisopropylethylamine → 5-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-methyl-N-(6-(pyrrolidin-1-yl)pyridin-3-yl)benzamide

HRID 541222

반응식

HRID 541222 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([CH:25]=3)[C:22](O)=[O:23])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:51]1([C:56]2[N:61]=[CH:60][C:59]([NH2:62])=[CH:58][CH:57]=2)[CH2:55][CH2:54][CH2:53][CH2:52]1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.CC#N.O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([CH:25]=3)[C:22]([NH:62][C:59]3[CH:60]=[N:61][C:56]([N:51]4[CH2:55][CH2:54][CH2:53][CH2:52]4)=[CH:57][CH:58]=3)=[O:23])=[O:16])[CH2:13][CH2:14]2)=[CH:7][CH:8]=1)#[N:2]

참가 물질

9

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 38991726-(Pyrrolidin-1-yl)pyridin-3-amine2회HCID 682883815-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-methylbenzoic acid

생성물 1

HCID 682889815-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-methyl-N-(6-(pyrrolidin-1-yl)pyridin-3-yl)benzamide수율 7%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매2회HCID 8857Ethyl Acetate용매

실험 절차

A mixture of compound 39.3 (528 mg, 1.52 mmol, 1.00 equiv) and HBTU (635 mg, 2.28 mmol, 1.50 equiv) in DMF (30 mL) was stirred for 30 min at room temperature. To this was added 6-(pyrrolidin-1-yl)pyridin-3-amine (compound 41.2, 299 mg, 1.82 mmol, 1.20 equiv) and DIEA (50 mg). The resulting mixture was stirred overnight at 60° C. in an oil bath. After cooling to room temperature, the reaction mixture was diluted with 50 mL of EtOAc and washed with 2×30 mL of NH4Cl (aq., sat.) followed by 2×30 mL of sodium bicarbonate (aq., sat.). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-016(Waters)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, Water with 50 mmol NH4HCO3 and CH3CN (10% CH3CN up to 32% in 3 min, up to 51% in 20 min, up to 100% in 1 min, down to 10% in 1 min); Detector, UV 220 NMnm. The fractions containing pure compound were combined and lyophilized to yield 50 mg (7%) of the title compound as a solid. m/z (ES+) 494 (M+H)+.

후처리

  1. stirringThe resulting mixture was stirred overnight at 60° C. in an oil bath
  2. temperatureAfter cooling to room temperature
  3. washwashed with 2×30 mL of NH4Cl (aq., sat.)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-016(Waters))
  7. waitup to 51% in 20 min
  8. waitup to 100% in 1 min
  9. waitdown to 10% in 1 min)
  10. additionThe fractions containing pure compound

출처 및 근거

ORD 기록
ord-4e65c340d9e1481892bbe069a8dd3c27
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871790B2

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