Hydrochloric Acid → HCID 59605427, compound

HRID 1945709Notes

Reaction equation

HRID 1945709 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[NH:29][CH:28]=1.Cl>O1CCOCC1>[N:27]1([C:2]2[N:3]=[C:4]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:13][CH2:14][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:16][CH2:17]4)=[CH:8][C:6]=3[N:7]=2)[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[N:29]=[CH:28]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 5798BenzimidazoleHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 59605427HCID 59605427, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]dimethylamine (50 mg, 0.13 mmol), benzimidazole (32 mg, 0.27 mmol) and concentrated HCl (53 μL, 0.64 mmol) in 1,4-dioxane (1 mL) was subjected to microwave irradiation at 150° C. for 40 min. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (2 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The eluent was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 95:5 to 90:10) to afford 110 as a white solid (38 mg, 63%). LCMS (Method F): RT=5.12 min, [M+H]+ 478.2. 1H NMR (CDCl3, 400 MHz): δ 9.04 (s, 1 H); 8.61-8.57 (m, 1 H); 7.86-7.82 (m, 1 H); 7.43-7.31 (m, 2 H); 7.27 (s, 1 H); 4.07 (t, J=4.8 Hz, 4 H); 3.92 (t, J=4.8 Hz, 4 H); 3.82 (s, 2 H); 3.08-2.99 (m, 2 H); 2.30 (s, 6 H); 2.20-2.10 (m, 3 H); 1.88-1.78 (m, 2 H); 1.66-1.54 (m, 2 H)

Workup

  1. customirradiation at 150° C. for 40 min
  2. washThe cartridge was then washed with MeOH
  3. washthe desired product was subsequently eluted
  4. customThe eluent was collected
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 95:5 to 90:10)

Sources & evidence

ORD record
ord-50c66e32616641ddae2891818d9644e0
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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