Triethylamine → (2e)-3-[4-Amino-3-(3-phenoxy-1-propynyl)thieno[3,2-c]pyridin-7-yl]-n-methylacrylamide

HRID 17124

Reaction equation

HRID 17124 reaction equation
Br[C:2]1[C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[C:10](I)[C:5]=2[S:4][CH:3]=1.[CH2:13]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:14]#[CH:15].[CH:23]1[CH:28]=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=C[CH:24]=1.CC[N:44]([CH2:47]C)CC.C[O:50]CCOC.O.C(O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:12][C:7]1[C:6]2[C:2]([C:15]#[C:14][CH2:13][O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:3][S:4][C:5]=2[C:10](/[CH:24]=[CH:23]/[C:28]([NH:44][CH3:47])=[O:50])=[CH:9][N:8]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 83613(Prop-2-ynyloxy)benzeneHCID 184507913-Bromo-7-iodothieno[3,2-C]pyridin-4-amineHCID 86587095Dimethoxyethane ethanol water

Product 1

HCID 11739996(2e)-3-[4-Amino-3-(3-phenoxy-1-propynyl)thieno[3,2-c]pyridin-7-yl]-n-methylacrylamideYield 27%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

A mixture of Example 21A (150 mg, 0.48 mmol), (2-propynyloxy)benzene (0.13 mL, 0.96 mmol), PdCl2(PPh3)2 (17 mg, 0.024 mmol), PPh3 (15 mg, 0.057 mmol), CuI (3 mg), and Et3N (1 mL, 7.2 mmol) in DME/water/ethanol (70:30:20 mixture, 2 mL) was heated in a sealed vial to 125° C. for 25 minutes with stirring in a Smith Synthesizer microwave oven (at 300 W). The reaction mixture was concentrated and the residue was purified by HPLC using the conditions described in Example 21C to provide 47 mg (27% yield) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 2.71 (d, J=4.6 Hz, 3H), 5.18 (s, 2H), 6.50 (d, J=16.0 Hz, 1H), 6.91 (s, 2H), 7.00 (t, J=7.4 Hz, 1H), 7.08 (dd, J=8.8, 0.9 Hz, 2H), 7.35 (dd, J=8.8, 7.4 Hz, 2H), 7.52 (d, J=16.0 Hz, 1H), 8.10-8.13 (m, 2H), 8.14 (s, 1H); MS (ESI(+)) m/e 364.0 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-e5a31fd4115d4791a984a247d56d9882
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Linked notes

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