Hydrochloric Acid → 4-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}pyrimidin-2-amine

HRID 1783813Notes

Reaction equation

HRID 1783813 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[N:31]5[C:27]([S:28][CH:29]=[CH:30]5)=[N:26][C:25]=4[C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([N+:38]([O-])=O)[CH:33]=4)[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl>C(O)C.O>[NH2:38][C:34]1[CH:33]=[C:32]([C:25]2[N:26]=[C:27]3[N:31]([C:24]=2[C:22]2[CH:21]=[CH:20][N:19]=[C:18]([NH:17][C@@H:13]4[CH2:14][CH2:15][CH2:16][N:11]([S:8]([C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=5)(=[O:10])=[O:9])[CH2:12]4)[N:23]=2)[CH:30]=[CH:29][S:28]3)[CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57463151N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-nitrophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine

Product 1

HCID 574631524-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}-4-[6-(3-nitrophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (1.05 g, 1.76 mmol) was dissolved in ethanol 95% (10 ml) and water (2.5 ml). The solution was treated with irn powder (1 g, 17.6 mmol) and concentrated HCl (200 uL). The reaction mixture was stirred at 100° C. for one hour. The mixture was cooled down and diluted with ethanol (100 ml). The heterogenous mixture was filtered over Celite and the volatiles were removed in vacuo. The residue was taken up in EtOAc (150 ml) and the organic phase was washed with a saturated aqueous NaHCO3 solution (2×100 ml), water (100 ml) and a saturated aqueous NaCl solution (100 ml). After drying over sodium sulfate and concentration, the solid was triturated in ether, giving the title compound as a yellow powder, 0.835 g (84%). M.p.=226-228° C. 400 MHz 1H NMR (DMSO-d6) δ: 8.73 (br. s, 1H), 8.10 (d, J=5.6 Hz, 1H), 7.77 (d, J=8.5 Hz, 2H), 7.67 (d, J=8.5 Hz, 2H), 7.36 (d, J=4.4 Hz, 1H), 7.09 (t, J=7.7 Hz, 1H), 7.02 (d, J=7.3 Hz, 1H), 6.81 (s, 1H), 6.69 (d, J=7.6 Hz, 1H), 6.65 (d, J=7.9 Hz, 1H), 6.49 (d, J=5.3 Hz, 1H), 5.01 (br. s, 2H), 4.02-3.88 (m, 1H), 3.73 (dd, J=11.1, 3.5 Hz, 1H), 3.47 (d, J=11.7 Hz, 1H), 2.60-2.46 (m, 1H), 2.39 (t, J=10.2 Hz, 1H), 1.98-1.80 (m, 2H), 1.68-1.51 (m, 1H), 1.47-1.32 (m, 1H). LCMS: 566 [M+H]. Calc. for C26H24N7O2S2Cl: C, 55.16; H, 4.27; N, 17.32. Found C, 54.98; H, 3.85; N, 17.23.

Workup

  1. temperatureThe mixture was cooled down
  2. filtrationThe heterogenous mixture was filtered over Celite
  3. customthe volatiles were removed in vacuo
  4. washthe organic phase was washed with a saturated aqueous NaHCO3 solution (2×100 ml), water (100 ml)
  5. dry with materialAfter drying over sodium sulfate and concentration
  6. customthe solid was triturated in ether

Sources & evidence

ORD record
ord-ac96b095864a48c1a97f17234f1daa49
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

Loading…