1,2-Dichloroethane → (E)-N-((3-ethyl-1H-indol-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamide

HRID 2097185Notes

Reaction equation

HRID 2097185 reaction equation
C(Cl)CCl.[CH2:5]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[CH2:16][NH:17][CH3:18])[CH3:6].Cl.[O:20]=[C:21]1[CH2:26][O:25][C:24]2[CH:27]=[C:28](/[CH:31]=[CH:32]/[C:33]([OH:35])=O)[CH:29]=[N:30][C:23]=2[NH:22]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:5]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[CH2:16][N:17]([CH3:18])[C:33](=[O:35])/[CH:32]=[CH:31]/[C:28]1[CH:29]=[N:30][C:23]2[NH:22][C:21](=[O:20])[CH2:26][O:25][C:24]=2[CH:27]=1)[CH3:6]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59277537(3-ethyl-1H-indol-2-yl)-N-methylmethanamineHCID 66967073(E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride

Product 1

HCID 16661419(E)-N-((3-ethyl-1H-indol-2-yl)methyl)-N-methyl-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylamideYield 42.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

EDC (116 mg, 0.6 mmol) was added to a solution of (3-ethyl-1H-indol-2-yl)-N-methylmethanamine (87 mg, 0.46 mmol), (E)-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid hydrochloride (123.65 mg, 1.05 mmol), HOBT.H2O (62 mg, 0.46 mmol) and DIPEA (0.33 mL, 1.8 mmol) in dry DMF (5 mL). After stirring overnight, water was added. The precipitate that formed was washed with ethyl acetate and dried to afford the title compound (76.2 mg, 42%). 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.18 (s, 1H), 7.88 (s, 1H), 7.46 (t, J=7.9 Hz, 2H), 7.25 (d, J=7.9 Hz, 1H), 7.03 (t, J=7.6 Hz, 1H), 6.95 (t, J=7.1 Hz, 2H), 4.92 (s, 2H), 4.90-4.74 (rotamers, s, 2H), 4.68 (s, 3H), 3.08 (m, 2H), 1.13 (t, J=7.4 Hz, 3H); MS (ESI): m/e 391.1 (C22H22N4O3+H)+.

Workup

  1. customThe precipitate that formed
  2. washwas washed with ethyl acetate
  3. customdried

Sources & evidence

ORD record
ord-9f1b9f6ece7747dbb09404f67f140de7
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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