Chlorotrimethylsilane → HCID 71084637, compound

HRID 1911038Notes

Reaction equation

HRID 1911038 reaction equation
[CH2:1]([O:5][C:6]1[C:13]([F:14])=[CH:12][C:11]([C:15]2[CH:16]=[N:17][CH:18]=[N:19][CH:20]=2)=[CH:10][C:7]=1[CH:8]=O)[CH2:2][CH:3]=[CH2:4].[NH2:21][C:22]([NH2:24])=[S:23].Cl[Si](C)(C)C>C(#N)C.CN(C=O)C.CCOC(C)=O>[F:14][C:13]1[C:6]2[O:5][CH2:1][CH2:2][C@@H:3]3[CH2:4][S:23][C:22]([NH2:24])=[N:21][C@@H:8]3[C:7]=2[CH:10]=[C:11]([C:15]2[CH:16]=[N:17][CH:18]=[N:19][CH:20]=2)[CH:12]=1

Participants

7

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 2723790ThioureaHCID 86685433HCID 86685433, compound

Product 1

HCID 71084637HCID 71084637, compoundYield 0.35%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(but-3-enyloxy)-3-fluoro-5-(pyrimidin-5-yl)benzaldehyde from step 4C (662 mg, 2.43 mmol) in acetonitrile (1.62 ml) and DMF (0.810 ml) was added thiourea (185 mg, 2.43 mmol) and chlorotrimethylsilane (0.311 ml, 2.43 mmol). The resulting mixture was brought to reflux and stirred for 1 h. The reaction mixture was then diluted with EtOAc (10 mL), washed with water (3×2 mL), brine (5 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by silica gel column chromatography (0-80% EtOAc/hexanes) gave the desired product (3.1 mg, 8.44 μmol, 0.35% yield). 1H NMR (500 MHz, methanol-d4) δ 7.63 (d, J=2.1 Hz, 1H), 7.57 (d, J=2.1 Hz, 2H), 6.03 (s, 1H), 5.99 (d, J=10.4 Hz, 1H), 3.12-3.01 (m, J=6.1, 6.1 Hz, 1H), 2.29-2.16 (m, J=4.6 Hz, 1H), 1.82 (d, J=1.2 Hz, 2H), 1.58 (t, J=12.1 Hz, 1H), 1.35 (dd, J=12.5, 3.1 Hz, 1H), 0.62-0.47 (m, 2H), 0.35-0.18 (m, 1H), −0.07-−0.31 (m, 1H). MS (ESI, M+H)+=331.16

Workup

  1. temperatureto reflux
  2. washwashed with water (3×2 mL), brine (5 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel column chromatography (0-80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5ef56dea81fe4904827bf2b6054060d3
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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