Hydrochloric Acid → HCID 59605904, compound

HRID 1945725Notes

Reaction equation

HRID 1945725 reaction equation
[N:1]1([C:7]2[C:8]3[S:28][C:27]([CH2:29][N:30]4[CH2:35][CH2:34][N:33]([C:36]([CH3:41])([CH3:40])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]4)=[CH:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[C:43]1[CH:52]=[CH:51][CH:50]=[C:49]2[C:44]=1[CH:45]=[CH:46][N:47]=[CH:48]2.O1CCOCC1.Cl>ClCCl.CCOCC.[I+].[Cu+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH:48]1[C:49]2[C:44](=[CH:43][CH:52]=[CH:51][C:50]=2[C:11]2[N:12]=[C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:8]3[S:28][C:27]([CH2:29][N:30]4[CH2:35][CH2:34][N:33]([C:36]([CH3:40])([CH3:41])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]4)=[CH:26][C:9]=3[N:10]=2)[CH:45]=[CH:46][N:47]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 7364875-BromoisoquinolineHCID 575067302-[4-(4-Morpholin-4-yl-2-(tributylstannanyl)-thieno[3,2-d]pyrimidin-6-ylmethyl)piperazin-1-yl]isobutyramide

Product 1

HCID 59605904HCID 59605904, compoundYield 7.8%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178505377HCID 178505377, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A microwave vessel was charged with 2-[4-(4-morpholin-4-yl-2-tributylstannanyl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazin-1-yl]-isobutyramide (0.200 g, 0.288 mmol), 5-bromoisoquinoline (0.072 g, 0.346 mmol), copper(I) iodine (0.066 g, 0.346 mmol), palladium tetrakis(triphenylphosphine) (0.033 g, 0.029 mmol) and dioxane (4 mL). The vessel was evacuated and back-filled with argon three times then sealed and heated at 140° C. under microwave irradiation for 20 min. The reaction mixture was cooled to room temperature and filtered through celite. The filtrates were concentrated then purified by chromatography (silica, 0 to 15% of a 9:1 MeOH:NH4OH mixture in dichloromethane) to give a yellow residue. This residue was dissolved in dichloromethane then 1 N HCl in ether (0.2 mL) added dropwise. The resulting precipitate was collected by filtration to furnish 135 (0.012 g, 6%) as a pale yellow powder and as a tetrahydrochloride salt. MS m/e 532 [M+H]+; 1H NMR (300 MHz, 360 K, DMSO-d6) δ ppm 1.49 (s, 6 H) 2.96-3.33 (m, 8 H) 3.79-3.91 (m, 4 H) 3.97-4.09 (m, 4 H) 4.22 (br. s., 2 H) 6.00 (br. s., 2 H) 7.65 (s, 1 H) 8.06-8.18 (m, 1 H) 8.23-8.35 (m, 2 H) 8.54 (d, J=7.5 Hz, 1 H) 8.68 (br. s., 1 H) 10.57 (br. s., 1 H)

Workup

  1. customThe vessel was evacuated
  2. additionback-filled with argon three times
  3. customthen sealed
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered through celite
  6. concentrationThe filtrates were concentrated
  7. customthen purified by chromatography (silica, 0 to 15% of a 9:1 MeOH:NH4OH mixture in dichloromethane)
  8. customto give a yellow residue
  9. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-f62d5be294d84a53862bf1aab8b3c847
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

Loading…