Sodium Carbonate → 4-(1-((2-(Isoquinolin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)morpholine

HRID 1922872Notes

Reaction equation

HRID 1922872 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[CH:30]1[C:39]2[CH:38]=[CH:37][CH:36]=[C:35](B(O)O)[C:34]=2[CH:33]=[CH:32][N:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(#N)C>[CH:30]1[C:39]2[C:34](=[C:35]([C:2]3[N:3]=[C:4]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[C:5]4[S:10][C:9]([CH2:11][N:12]5[CH2:17][CH2:16][CH:15]([N:18]6[CH2:23][CH2:22][O:21][CH2:20][CH2:19]6)[CH2:14][CH2:13]5)=[CH:8][C:6]=4[N:7]=3)[CH:36]=[CH:37][CH:38]=2)[CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 599474Isoquinoline-5-boronic acidHCID 574939772-Chloro-4-morpholin-4-yl-6-(4-morpholin-4-yl-piperidin-1-ylmethyl)-thieno[3,2-d]pyrimidine

Product 1

HCID 498340414-(1-((2-(Isoquinolin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)morpholineYield 27.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

A sealable tube was charged with 2-chloro-4-morpholin-4-yl-6-(4-morpholin-4-yl-piperidin-1-ylmethyl)-thieno[3,2-d]pyrimidine (0.100 g, 0.229 mmol), isoquinoline-5-boronic acid (0.048 g, 0.275 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.008 g, 0.012 mmol), 1 N aqueous sodium carbonate solution (1 mL) and acetonitrile (3 mL). The vessel was evacuated and back-filled with argon three times then sealed and heated at 130° C. for 90 min. The reaction mixture was cooled, concentrated, redissolved in ethyl acetate and filtered through celite. The filtrates were concentrated then purified by chromatography (silica, 10 to 20% methanol in dichloromethane) to give 101 (0.033 g, 27%) as a yellow solid. MS m/e 531 [M+H]+; 1H NMR (300 MHz, CDCl3) δ ppm 1.54 - 1.71 (m, 2 H) 1.87 (d, J=11.3 Hz, 2 H), 2.09-2.30 (m, 3 H), 2.52-2.63 (m, 4 H) 3.01-3.11 (m, 2 H) 3.70-3.78 (m, 4 H) 3.85 (s, 2 H) 3.87-3.94 (m, 4 H) 4.03-4.12 (m, 4 H) 7.35 (s, 1 H), 7.67-7.75 (m, 1 H) 8.06 (d, J=8.3 Hz, 1 H) 8.31-8.37 (m, 1 H) 8.52-8.58 (m, 1 H) 8.61-8.67 (m, 1 H) 9.30 (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
  5. concentrationconcentrated
  6. dissolutionredissolved in ethyl acetate
  7. filtrationfiltered through celite
  8. concentrationThe filtrates were concentrated
  9. customthen purified by chromatography (silica, 10 to 20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-88a64f2f1bdd491ea4a694a5fb1d8f61
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…