Acetic Acid → 4-(1-((2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)morpholine

HRID 1922935Notes

Reaction equation

HRID 1922935 reaction equation
[N:1]1([C:7]2[C:8]3[S:23][C:22]([CH2:24][N:25]4[CH2:28][CH:27]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:26]4)=[CH:21][C:9]=3[N:10]=[C:11]([NH:13][C:14]3[C:15]([NH2:20])=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:35](O)(=O)[CH3:36]>>[CH3:35][C:36]1[N:13]([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:23][C:22]([CH2:24][N:25]4[CH2:28][CH:27]([N:29]5[CH2:30][CH2:31][O:32][CH2:33][CH2:34]5)[CH2:26]4)=[CH:21][C:9]=3[N:10]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N:20]=1

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 59606113N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine

Product 1

HCID 596052834-(1-((2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)morpholineYield 43%

Conditions

Temperature
120 °C

Procedure

A mixture of N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine (100 mg, 0.21 mmol) and glacial acetic acid (0.5 mL) was heated at 120° C. for 3 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 product 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 reversed phase HPLC (Phenomenex Luna C-18, 20 mM Et3N in water on a gradient of 20 mM Et3N in acetonitrile 95:5 to 2:98) to afford 172 as a white solid (45 mg, 43%). LCMS (method A): RT=5.65 min, M+H−=506.1. 1H NMR (CDCl3, 400 MHz) δ 8.08-8.03 (m, 1 H), 7.73-7.68 (m, 1 H), 7.30-7.26 (m, 3 H), 4.05 (t, J=4.8 Hz, 4 H), 3.99 (s, 2 H), 3.88 (t, J=4.8 Hz, 4 H), 3.73 (m, 4 H), 3.65 (s, 2 H), 3.18-2.99 (m, 3 H), 2.93 (s, 3 H), 2.34 (m, 4 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 product 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-f6461424a1dd4697aa1acdf0070d1f80
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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