3-Butyn-1-OL → n-{4-[4-Amino-7-(4-hydroxy-1-butynyl)thieno[3,2-c]pyridin-3-yl]phenyl}-n'-(3-methylphenyl)urea

HRID 17135

Reaction equation

HRID 17135 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=4)=[O:19])=[CH:13][CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](I)=[CH:4][N:3]=1.[CH2:29]([OH:33])[CH2:30][C:31]#[CH:32]>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=4)=[O:19])=[CH:13][CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32]#[C:31][CH2:30][CH2:29][OH:33])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 135663-Butyn-1-OLHCID 18451300n-[4-(4-Amino-7-iodothieno [3,2-c]pyridin-3-yl)phenyl]-n'-(3-methylphenyl)urea

Product 1

HCID 18451246n-{4-[4-Amino-7-(4-hydroxy-1-butynyl)thieno[3,2-c]pyridin-3-yl]phenyl}-n'-(3-methylphenyl)ureaYield 82.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of Example 144A (0.227 g, 0.45 mmol) in piperidine (3 mL) was degassed by bubbling nitrogen through the suspension for 5 minutes, treated with 3-butyn-1-ol (0.069 mL, 0.91 mmol), Pd(PPh3)4 (26 mg, 0.023 mmol), and CuI (5 mg, 0.023 mmol), then heated to 80° C. in a sealed tube for 30 minutes. The resulting homogeneous solution was cooled to room temperature and concentrated under a stream of nitrogen. The residue was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane to provide 164 mg (81%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.29 (s, 3H), 2.65 (t, J=6.78 Hz, 2H), 3.63 (q, J=6.73 Hz, 2H), 4.92 (t, J=5.59 Hz, 1H), 5.70 (s, 2H), 6.81 (d, J=7.46 Hz, 1H), 7.17 (t, J=7.80 Hz, 1H), 7.25-7.28 (m, 1H), 7.32 (s, 1H), 7.37 (d, J=8.48 Hz, 2H), 7.49 (s, 1H), 7.60 (d, J=8.48 Hz, 2H), 7.93 (s, 1H), 8.65 (s, 1H), 8.85 (s, 1H); MS (ESI(+)) m/e 443 (M+H)+.

Workup

  1. customby bubbling nitrogen through the suspension for 5 minutes
  2. temperatureThe resulting homogeneous solution was cooled to room temperature
  3. concentrationconcentrated under a stream of nitrogen
  4. customThe residue was purified by flash column chromatography on silica gel with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-ccc1c25f7e344939bb02411da993f400
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Linked notes

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