1,2-Dichloroethane → (E)-N-(3-cyano-1H-indol-2-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-acrylamide

HRID 1362355

Reaction equation

HRID 1362355 reaction equation
C(Cl)CCl.Cl.[O:6]=[C:7]1[NH:16][C:15]2[N:14]=[CH:13][C:12]([CH:17]=[CH:18][C:19]([OH:21])=O)=[CH:11][C:10]=2[CH2:9][CH2:8]1.[CH3:22][NH:23][CH2:24][C:25]1[NH:26][C:27]2[C:32]([C:33]=1[C:34]#[N:35])=[CH:31][CH:30]=[CH:29][CH:28]=2.C1C=CC2N(O)N=NC=2C=1.O.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:34]([C:33]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:26][C:25]=1[CH2:24][N:23]([CH3:22])[C:19](=[O:21])/[CH:18]=[CH:17]/[C:12]1[CH:13]=[N:14][C:15]2[NH:16][C:7](=[O:6])[CH2:8][CH2:9][C:10]=2[CH:11]=1)#[N:35]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 592775892-methylaminomethyl-1H-indole-3-carbonitrileHCID 669053063-(7-Oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)acrylic acid hydrochloride

Product 1

HCID 16660303(E)-N-(3-cyano-1H-indol-2-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-acrylamideYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

EDC (250 mg, 1.3 mmol) was added to a solution of 3-(7-Oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-acrylic acid hydrochloride (267 mg, 1.05 mmol), 2-methylaminomethyl-1H-indole-3-carbonitrile (186 mg, 1.0 mmol), HOBt H2O (135 mg, 1.0 mmol) and DIPEA (510 μL, 3.0 mmol) in dry DMF (4 mL). After 3 days of stirring, the mixture was diluted with water (50 mL) at 10° C. The precipitate was filtered, washed with water and dried. The solid was stirred in MeOH (10 mL), filtered and dried to afford 239 mg (62%) title compound. 1H NMR (300 MHz, DMSO-d6, δ): 12.28 and 12.09 (rotamers, 2s, 1H), 10.66 (s, 1H), 8.37 (s, 1H), 8.11 and 8.05 (rotamers, 2s, 1H), 7.52 (m, 3H), 7.22 (m, 3H), 5.13 and 4.90 (rotamers, 2s, 2H), 3.27 and 2.97 (rotamers, 2s, 3H), 2.92 (m, 2H), 2.55 (m, 2H). MS (ESI): nm/e 386 (M+H)+.

Workup

  1. filtrationThe precipitate was filtered
  2. washwashed with water
  3. customdried
  4. stirringThe solid was stirred in MeOH (10 mL)
  5. filtrationfiltered
  6. customdried

Sources & evidence

ORD record
ord-0f503549cde049e3a2788cb495956986
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Linked notes

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