4-Methylmorpholine → N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamide

HRID 602091노트

반응식

HRID 602091 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:17]1[C:22]2[CH2:23][CH2:24][O:25][CH2:26][C:21]=2[CH:20]=[N:19][C:18]=1[N:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]1.CCN=C=NCCCN(C)C.[CH:45]1[CH:46]=[CH:47][C:48]2[N:53](O)N=N[C:49]=2[CH:50]=1.CN1CCOCC1>O.CC(N(C)C)=O>[N:17]1[C:22]2[CH2:23][CH2:24][O:25][CH2:26][C:21]=2[CH:20]=[N:19][C:18]=1[N:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:12](=[O:14])[C:11]2[CH:15]=[CH:16][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)[CH2:29][CH2:28]1.[CH3:47][CH:48]1[CH:49]=[CH:50][CH:45]([CH3:46])[N:53]1[C:26]([C:21]1[CH:22]=[CH:23][C:18]([N:27]2[CH2:28][CH2:29][CH:30]([NH:33][C:12](=[O:14])[C:11]3[CH:15]=[CH:16][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[N:9][CH:10]=3)[CH2:31][CH2:32]2)=[N:19][CH:20]=1)=[O:25]

참가 물질

9

반응물 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 247299726-(3-Fluorophenyl)nicotinic acidHCID 670066751-(7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-amine

생성물 2

HCID 59743688N-[1-(7,8-Dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-yl]-6-(3-fluorophenyl)nicotinamideHCID 67267283N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamide수율 154.4%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

실험 절차

To a vial was added, 6-(3-fluorophenyl)nicotinic acid (46.4 mg, 0.213 mmol), 1-(7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-amine (50 mg, 0.21 mmol), EDAC (45.0 mg, 0.235 mmol), HOBT (28.8 mg, 0.213 mmol), and DMA (1 mL) followed by NMM (0.058 mL, 0.534 mmol). The reaction was stirred overnight at room temperature and then diluted with H2O and the resulting solid filtered and collected to give the desired product, N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamide (81 mg, 88%). 1H NMR (400 MHz, DMSO-d6) □ ppm 9.06 (1H, s), 8.45 (1H, d, J=7.5 Hz), 8.21-8.30 (1H, m), 8.04-8.14 (2H, m), 7.89-8.02 (2H, m) 7.49-7.59 (1H, m), 7.29 (1H, t), 4.49-4.64 (5H, m), 4.11 (1H, br. s.), 3.89 (2H, t, J=5.9 Hz), 2.94-3.07 (2 H, m), 1.88 (2H, d, J=10.1 Hz), 1.42-1.56 (3H, m). HRMS (TOF, ES+) calculated for M+H: 434.1992; observed 434.2165.

후처리

  1. additionTo a vial was added
  2. filtrationthe resulting solid filtered
  3. customcollected

출처 및 근거

ORD 기록
ord-8ea38fdfeafe4f70a337c3e7e2eaa897
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902373B2

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