Potassium Carbonate → HCID 57590652, compound

HRID 1783817Notes

Reaction equation

HRID 1783817 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:10]2[N:11]=[C:12]3[N:16]([C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C@@H:25]4[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]4)[N:19]=2)[CH:15]=[CH:14][S:13]3)[CH:7]=[CH:8][CH:9]=1.CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:57][C@@H:58]2[CH2:62][O:61][C:60]([CH3:64])([CH3:63])[O:59]2)(=O)=O)=CC=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:63][C:60]1([CH3:64])[O:59][C@H:58]([CH2:57][N:27]2[CH2:28][CH2:29][CH2:30][C@@H:25]([NH:24][C:20]3[N:19]=[C:18]([C:17]4[N:16]5[C:12]([S:13][CH:14]=[CH:15]5)=[N:11][C:10]=4[C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH3:2])[CH:5]=4)[CH:23]=[CH:22][N:21]=3)[CH2:26]2)[CH2:62][O:61]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-ToluenesulfonateHCID 67519766HCID 67519766, compound

Product 1

HCID 57590652HCID 57590652, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

The 4-[6-(3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[(3R)-piperidin-3-yl]-pyrimidin-2-amine hydrochloride (310 mg, 0.7 mmol) was dissolved in DMF (15 ml) and was treated successively with Hunig's base (240 uL, 1.4 mmol), potassium carbonate (192 mg, 0.7 mmol) and terabutylammonium iodide (26 mg, 0.07 mmol). The mixture was heated to 130° C. and the [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methyl-benzenesulfonate (0.2 g, 0.7 mmol) was added in three portions. The mixture was kept at 130° C. for 5 hours, at which point no more starting material appears by HPLC. The volatiles were removed in vacuo and the residue was taken up in ether (100 ml). The organic phase was washed with water (2×20 ml) and with an aqueous sodium chloride solution (20 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow oil. The product was purified by flash chromatography (5:4:0.5 hexanes/EtOAc, MeOH), affording the title compound as an off-white solid (231 mg, 64%). M.p.=73-75° C. 400 MHz 1H NMR (DMSO-d6) δ: 8.71 (br. s, 1H), 8.07 (d, J=5.1 Hz, 1H), 7.42 (d, J=4.4 Hz, 1H), 7.36 (t, J=7.9 Hz, 1H), 7.19-7.11 (m, 2H), 7.04-6.92 (m, 2H), 6.36 (d, J=5.1 Hz, 1H), 4.19 (quintet, J=6.2 Hz, 1H), 3.99 (dd, J=8.1, 6.2 Hz, 1H), 3.96-3.87 (m, 1H), 3.77 (s, 3H), 3.52 (t, J=7.5 Hz, 1H), 3.15 (s, 2H), 3.05 (d, J=9.9 Hz, 1H), 2.69 (d, J=10.3 Hz, 1H), 2.15 (t, J=9.4 Hz, 1H), 2.04 (t, J=9.5 Hz, 1H), 1.90-1.82 (m, 1H), 1.75-1.65 (m, 1H), 1.59-1.48 (m, 1H), 1.40-1.25 (m, 1H), 1.29 (s, 3H), 1.21 (s, 3H). LCMS: 521 [M+H].

Workup

  1. customThe volatiles were removed in vacuo
  2. washThe organic phase was washed with water (2×20 ml) and with an aqueous sodium chloride solution (20 ml)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customgiving a yellow oil
  6. customThe product was purified by flash chromatography (5:4:0.5 hexanes/EtOAc, MeOH)

Sources & evidence

ORD record
ord-1b9ef12bac9d499db99b9775ca0b332b
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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