Sodium Carbonate → 2-(4-((2-(1-Acetamidoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide

HRID 1945734Notes

Reaction equation

HRID 1945734 reaction equation
C([N:4]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](Br)=[CH:10][N:9]=1)[C:5](=[O:7])[CH3:6])(=O)C.Cl[C:20]1[N:21]=[C:22]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[C:23]2[S:28][C:27]([CH2:29][N:30]3[CH2:35][CH2:34][N:33]([C:36]([CH3:41])([CH3:40])[C:37]([NH2:39])=[O:38])[CH2:32][CH2:31]3)=[CH:26][C:24]=2[N:25]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:5]([NH:4][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:20]2[N:21]=[C:22]([N:42]3[CH2:43][CH2:44][O:45][CH2:46][CH2:47]3)[C:23]3[S:28][C:27]([CH2:29][N:30]4[CH2:31][CH2:32][N:33]([C:36]([CH3:41])([CH3:40])[C:37]([NH2:39])=[O:38])[CH2:34][CH2:35]4)=[CH:26][C:24]=3[N:25]=2)=[CH:10][N:9]=1)(=[O:7])[CH3:6]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 574940122-(4-((2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamideHCID 59605275N-acetyl-N-(4-bromoisoquinolin-1-yl)acetamide

Product 1

HCID 596057642-(4-((2-(1-Acetamidoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamideYield 22%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Following General Procedure B of Suzuki coupling, N-acetyl-N-(4-bromoisoquinolin-1-yl)acetamide (57 mg) was reacted with 2-(4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide (107 mg). After reaction completion, 1 M Na2CO3 (2 mL) and 1,4-dioxane (2 mL) were added to the mixture. The suspension was heated at 60° C. for 3 h. The reaction mixture was concentrated. Water (5 mL) was added. The contents were extracted with DCM (2×10 mL). The combined DCM solutions were dried (Na2SO4). The crude was purified with reverse-phase HPLC to give 144 (20 mg, 22%). LCMS: M+H+=589. 1H NMR (400 MHz, CDCl3) δ 8.86 (2H), 8.07 (, s, br, 2H), 7.75 (t, J=7.7, 1H), 7.64 (t, J=7.6, 1H), 7.36 (s, 1H), 7.09 (s, 1H), 5.18 (s, 1H), 4.12-4.00 (m, 4H), 3.94-3.81 (m, 6H), 2.62 (s, 8H), 2.44 (s, 3H), 1.25 (s, 6H)

Workup

  1. additionwere added to the mixture
  2. concentrationThe reaction mixture was concentrated
  3. additionWater (5 mL) was added
  4. extractionThe contents were extracted with DCM (2×10 mL)
  5. dry with materialThe combined DCM solutions were dried (Na2SO4)
  6. customThe crude was purified with reverse-phase HPLC

Sources & evidence

ORD record
ord-a6f1cc35b3c94283b26b35d98bb6b897
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

Loading…