Acetic Acid → 2-(3,4-Dimethoxy-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-5-yl]-imidazo[2,1-b][1,3,4]thiadiazole

HRID 2409557Notes

Reaction equation

HRID 2409557 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([N:25]5[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]5)=[N:23][CH:24]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH3:31]CN(CC)CC.C=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([N:25]5[CH2:26][CH2:27][N:28]([CH3:31])[CH2:29][CH2:30]5)=[N:23][CH:24]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 667169502-(3,4-Dimethoxy-phenyl)-5-(2-piperazin-1-yl-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 667172802-(3,4-Dimethoxy-phenyl)-5-[2-(4-methyl-piperazin-1-yl)-pyrimidin-5-yl]-imidazo[2,1-b][1,3,4]thiadiazoleYield 12.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 2-(3,4-Dimethoxy-phenyl)-5-(2-piperazin-1-yl-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazole (52 mg, 0.113 mmol, 1 eq), Et3N (0.032 mL, 0.226 mmol, 2 eq), formaldehyde (0.102 mL, 1.36 mmol, 12 eq) and acetic acid (0.02 mL, 0.136 mmol, 1.2 eq) in MeOH (2 mL) was added Sodium cyanoborohydride (0.1 g, 1.58 mmol, 14 eq). The reaction mixture was stirred at rt for 2 h. Solvents were evaporated to dryness and the residue was dissolved in sat NaHCO3/EtOAc. Layers were separated and the aqueous layer was extracted once with EtOAc. The combined organic layers were dried, filtered and evaporated. The residue was purified by HPLC to give the desired product (6 mg, 12%). HPLC-MS: (5-40% B in 8 min, 0.8 mL/min, 50° C.): tR=4.64 min, [M+H]+ m/z 438.2; 1H NMR (300 MHz, DMSO) δ 8.98 (s, 2H), 7.70 (s, 1H), 7.56 (dd, J=8.4, 2.0 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.80 (m, 4H), 2.38 (m, 4H), 2.22 (s, 3H).

Workup

  1. customSolvents were evaporated to dryness
  2. dissolutionthe residue was dissolved in sat NaHCO3/EtOAc
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted once with EtOAc
  5. customThe combined organic layers were dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-5a49a1afaa8b400bae2498d7500b1cb2
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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