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 602091

反応式

HRID 602091 の反応式
[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]

参加物

9

反応物 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

生成物 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)nicotinamide収率 154.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-8ea38fdfeafe4f70a337c3e7e2eaa897
出典データセット
uspto-grants-2011_03
特許番号
US07902373B2

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