Triethylamine → 4-(4-Chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-1,3-dihydro-indol-2-one

HRID 857433Notes

Reaction equation

HRID 857433 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:11])[NH:6]2.[F:12][C:13]([F:23])([F:22])[C:14]1[C:15]([Cl:21])=[N:16][C:17](Cl)=[N:18][CH:19]=1.ClCCCl.C(O)(C)(C)C.CCN(CC)CC>CCOCC.[Cl-].[Cl-].[Zn+2]>[Cl:21][C:15]1[C:14]([C:13]([F:22])([F:12])[F:23])=[CH:19][N:18]=[C:17]([NH:1][C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[CH2:4][C:5](=[O:11])[NH:6]3)[N:16]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 122374724-Aminoindolin-2-oneHCID 21868497Tert-butyl alcohol 1,2-dichloroethane2×

Product 1

HCID 218684954-(4-Chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent

Procedure

4-amino-oxindole (2.75 g, 18.6 mmol) was added portionwise to a solution of 5-trifluoromethyl-2,4-dichloropyrimidine (4.03 g, 1 eq) and ZnCl2 (18.6 mL of a 1M solution in ether) in 1:1 DCE/t-butanol (60 mL) at 0° C. After 15 minutes a solution of Et3N (2.85 mL, 1.1 eq) in 1:1 DCE/t-butanol (20 mL) was added dropwise. The reaction was allowed to warm to RT overnight. The reaction was then concentrated and the product triturated from methanol as a grey solid 3.05 g (50%). 1H NMR (DMSO-d6, 400 MHz) δ 3.43 (s, 2H), 6.64 (m, 1H), 7.14 (m, 2H), 8.74 (s, 1H), 10.32 (s, 1H), 10.43 (s, 1H); HPLC ret. time: 5.859 min. LRMS (M+) 329.1, 331.0.

Workup

  1. concentrationThe reaction was then concentrated
  2. customthe product triturated from methanol as a grey solid 3.05 g (50%)

Sources & evidence

ORD record
ord-964c7a44021f4394b751050cfae5b1e4
Source dataset
uspto-grants-2006_12
Patent number
US07145008B2

Reaction notes

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