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

HRID 1710564Notes

Reaction equation

HRID 1710564 reaction equation
C(Cl)CCl.[O:5]1[CH2:10][CH2:9][NH:8][C:7]2[N:11]=[CH:12][C:13](/[CH:15]=[CH:16]/[C:17]([OH:19])=O)=[CH:14][C:6]1=2.[CH3:20][N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]1[CH2:30][NH:31][CH3:32].C1C=CC2N(O)N=NC=2C=1.O.CCN(CC)CC>CN(C=O)C>[O:5]1[CH2:10][CH2:9][NH:8][C:7]2[N:11]=[CH:12][C:13](/[CH:15]=[CH:16]/[C:17]([N:31]([CH3:32])[CH2:30][C:22]3[N:21]([CH3:20])[C:29]4[C:24]([CH:23]=3)=[CH:25][CH:26]=[CH:27][CH:28]=4)=[O:19])=[CH:14][C:6]1=2

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 22139122(E)-3-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)acrylic acid

Product 1

HCID 9820375(E)-3-(3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamideYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (230 mg, 1.2 mmole) was added to a solution (E)-3-(3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazin-7-yl)acrylic acid (206 mg, 1.0 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (209 mg, 1.2 mmole), HOBt.H2O (162 mg, 1.2 mmole), and Et3N (0.21 mL, 1.5 mmole) in dry DMF (5 mL) at RT. After 18 hr the mixture was concentrated. Flash chromatography on silica gel (5% EtOH/EtOAc) gave the title compound (238 mg, 66%) as a yellow solid: 1H NMR (400 MHz, d6-DMSO) δ 7.99-6.95 (m, 8H), 6.40 (s, 1H), 4.82 (s, 2H), 4.11 (bs, 2H), 3.72 (bs, 3H), 3.67 (bs, 2H), 3.08 (s, 3H); for minor rotomer δ 6.15 (s, 1H), 5.02 (s, 2H), 2.96 (s, 3H); MS (ES) m/e 363 (M+H)+.

Workup

  1. customat RT
  2. concentrationAfter 18 hr the mixture was concentrated

Sources & evidence

ORD record
ord-10239a7e42c04709bb4e402e13c4f7e6
Source dataset
uspto-grants-2010_09
Patent number
US07790716B2

Reaction notes

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