Triethylamine → 1-(3-(3-Cyano-4-fluorophenyl)-3-methyl-2-oxobutyl)-3-(4-fluoro-3-methoxyphenyl)thiourea

HRID 83884Notes

Reaction equation

HRID 83884 reaction equation
Cl.[NH2:2][CH2:3][C:4](=[O:17])[C:5]([C:8]1[CH:9]=[CH:10][C:11]([F:16])=[C:12]([CH:15]=1)[C:13]#[N:14])([CH3:7])[CH3:6].CCN(CC)CC.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]=[C:33]=[S:34])=[CH:28][C:27]=1[O:35][CH3:36]>C(Cl)Cl>[C:13]([C:12]1[CH:15]=[C:8]([C:5]([CH3:7])([CH3:6])[C:4](=[O:17])[CH2:3][NH:2][C:33]([NH:32][C:29]2[CH:30]=[CH:31][C:26]([F:25])=[C:27]([O:35][CH3:36])[CH:28]=2)=[S:34])[CH:9]=[CH:10][C:11]=1[F:16])#[N:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 265982444-Fluoro-3-methoxyphenylisothiocyanateHCID 667404015-(4-Amino-2-methyl-3-oxobutan-2-yl)-2-fluorobenzonitrile hydrochloride

Product 1

HCID 866622561-(3-(3-Cyano-4-fluorophenyl)-3-methyl-2-oxobutyl)-3-(4-fluoro-3-methoxyphenyl)thioureaYield 84.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 5-(4-amino-2-methyl-3-oxobutan-2-yl)-2-fluorobenzonitrile hydrochloride (2.8 g, 10.9 mmol) in DCM (50 mL) were added Et3N (4.6 mL, 32.7 mmol, 3 eq) and 1-fluoro-4-isothiocyanato-2-methoxybenzene (2.2 g, 12 mmol, 1.1 eq). After stirring 2 h, the reation mixture was partitioned in DCM and water. The organic layer was separated, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography (silica, Hex:EA=1:1) to give 1-(3-(3-cyano-4-fluorophenyl)-3-methyl-2-oxobutyl)-3-(4-fluoro-3-methoxyphenyl)thiourea (3.7 g, 84%). 1H NMR (400 MHz, CDCl3) δ 7.59 (bs, 1H), 7.53-7.49 (m, 2H), 7.26-7.18 (m, 2H), 6.89-6.79 (m, 2H), 6.70 (bs, 1H), 4.44 (d, J=4.4 Hz, 2H), 3.90 (s, 3H), 1.58 (s, 6H).

Workup

  1. customthe reation mixture was partitioned in DCM
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was purified by flash column chromatography (silica, Hex:EA=1:1)

Sources & evidence

ORD record
ord-42ce718e7cbd41078e74ec8a3227f296
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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