Ethyl orthoformate → HCID 57506741, compound

HRID 1922886Notes

Reaction equation

HRID 1922886 reaction equation
[CH3:1][N:2]([CH3:33])[CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[S:18][C:17]3[C:16]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[N:15][C:14]([NH:25][C:26]4[C:27]([NH2:32])=[CH:28][CH:29]=[CH:30][CH:31]=4)=[N:13][C:12]=3[CH:11]=2)[CH2:5][CH2:4]1.C(OCC)(OCC)O[CH2:36][CH3:37]>CN(C=O)C>[CH3:1][N:2]([CH3:33])[CH:3]1[CH2:4][CH2:5][N:6]([CH2:9][C:10]2[S:18][C:17]3[C:16]([N:19]4[CH2:20][CH2:21][O:22][CH2:23][CH2:24]4)=[N:15][C:14]([N:25]4[C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[N:32]=[C:36]4[CH3:37])=[N:13][C:12]=3[CH:11]=2)[CH2:7][CH2:8]1

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 57506742HCID 57506742, compound

Product 1

HCID 57506741HCID 57506741, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of N-[6-(4-dimethylaminopiperidin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine (80 mg, 0.17 mmol) and triethyl orthoformate (1 mL, 6.0 mmol) in DMF (1 mL) was heated at 150° C. for 6 h. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 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) followed by reverse phase HPLC (Phenomenex Luna C18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 117 as a white solid (20 mg, 24%). LCMS (Method F): RT=4.24 min, [M+H]+ 492.3. 1H NMR (CDCl3, 400 MHz): δ 8.09-8.04 (m, 1 H); 7.74-7.68 (m, 1 H); 7.29-7.24 (m, 3 H); 4.08-4.02 (m, 4 H); 3.91-3.86 (m, 4 H); 3.83 (s, 2 H); 3.08-3.00 (m, 2 H); 2.93 (s, 3 H); 2.30 (s, 6 H); 2.21-2.10 (m, 3 H); 1.88-1.79 (m, 2 H); 1.68-1.53 (m, 2 H)

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  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)

Sources & evidence

ORD record
ord-c488646011104bf2b1609776be5a5b6e
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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