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 2097103

Reaction equation

HRID 2097103 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.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 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 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 962WaterSolvent2×HCID 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. NMR (300 MHz, DMSO-d6, 8): 12.28 and 12.09 (rotamers, 2 s, 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): m/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-cb01943190a24971b92afe19c0281dcb
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Linked notes

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