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 1921043Notes

Reaction equation

HRID 1921043 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, 3 H); 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-ba6cb135a8044ab89cf57e6145d8afab
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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