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 225914Notes

Reaction equation

HRID 225914 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-(3,4dihydro-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, 8 H), 6.40 (s, 1 H), 4.82 (s, 2 H), 4.11 (bs, 2 H), 3.72 (bs, 3 H), 3.67 (bs, 2 H), 3.08 (s, 3 H); for minor rotomer δ 6.15 (s, 1 H), 5.02 (s, 2 H), 2.96 (s, 3 H); MS (ES) m/e 363 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-38c6b1fb6db742a4894be021842bb57f
Source dataset
uspto-grants-2009_07
Patent number
US07557125B2

Reaction notes

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