Trifluoroacetic acid → 6-(2-chloro-4-(1,3,4-oxadiazol-2-yl)phenyl)-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 387219Notes

Reaction equation

HRID 387219 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]1[C:35](=[O:36])[N:34]([CH2:37][CH3:38])[C:15]2[N:16]=[C:17]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)=[CH:23][CH:22]=3)[N:18]=[CH:19][C:14]=2[CH:13]=1)[C:5]([NH:7][NH2:8])=[O:6].F[C:40](F)(F)C(O)=O>C(OCC)(OCC)OCC>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][CH:40]=[N:8][N:7]=2)[CH:9]=[CH:10][C:11]=1[C:12]1[C:35](=[O:36])[N:34]([CH2:37][CH3:38])[C:15]2[N:16]=[C:17]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([N:27]4[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]4)=[CH:25][CH:26]=3)[N:18]=[CH:19][C:14]=2[CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 671196213-Chloro-4-{8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl}benzoic acid hydrazide

Product 1

HCID 513542406-(2-chloro-4-(1,3,4-oxadiazol-2-yl)phenyl)-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 31214Ethyl orthoformateSolvent

Conditions

Temperature
130 °C

Procedure

3-Chloro-4-{8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl}benzoic acid hydrazide (7, 30 mg, 0.06 mmol) was suspended in triethyl orthoformate (5 mL) to which was added trifluoroacetic acid (1 mL). The resulting reaction mixture was heated at 130° C. for 2 h. The volatiles were removed and the residue was taken up in dichloromethane (1×20 mL) and washed with 10% sodium hydroxide solution (2×10 mL). The organic layer was dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography using dichloromethane:methanol (95:5). The title compound (18 mg, 0.03 mmol, 50%) was obtained as a yellow solid. ESMS m/z 543 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.57 (s, 1H) 8.50 (s, 1H) 8.21 (d, J=1.5 Hz, 1H) 8.04 (dd, J=8.0, 1.5 Hz, 1H) 7.62 (s, 1H) 7.52-7.60 (m, 3H) 7.29 (br. s., 1H) 6.98 (d, J=9.0 Hz, 2H) 4.50 (q, J=6.8 Hz, 2H) 3.16-3.27 (m, 4H) 2.56-2.65 (m, 4H) 2.37 (s, 3H) 1.39 (d, J=6.8 Hz, 3H).

Workup

  1. customThe resulting reaction mixture
  2. customThe volatiles were removed
  3. washwashed with 10% sodium hydroxide solution (2×10 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f0ea3ee6287b470690f1e2aacb091cfe
Source dataset
uspto-grants-2013_02
Patent number
US08372970B2

Reaction notes

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