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 602091Notes

Reaction equation

HRID 602091 reaction equation
[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]

Participants

9

Reactant 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

Product 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)nicotinamideYield 154.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-8ea38fdfeafe4f70a337c3e7e2eaa897
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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