Triethylamine → 4-Methyl-piperazine-1-carboxylic acid [2-((R)-indan-1-ylamino)-quinolin-6-yl]-amide

HRID 1928719Notes

Reaction equation

HRID 1928719 reaction equation
[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH2:21])[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(Cl)(O[C:33](=[O:39])OC(Cl)(Cl)Cl)Cl.[CH3:41][N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1>O1CCCC1>[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:21][C:33]([N:45]4[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]4)=[O:39])[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 531671-MethylpiperazineHCID 94429TriphosgeneHCID 57860958(R)-N2-Indan-1-yl-quinoline-2,6-diamine

Product 1

HCID 442174734-Methyl-piperazine-1-carboxylic acid [2-((R)-indan-1-ylamino)-quinolin-6-yl]-amideYield 118.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

(R)—N2-Indan-1-yl-quinoline-2,6-diamine (0.25 g, 0.9 mmol) was dissolved in tetrahydrofuran (10 mL) and triethylamine (0.138 mL, 1.0 mmol) was added. At 0° C. triphosgene (121 mg, 0.4 mmol) was added and the reaction mixture subsequently heated to 80° C. for 3 h. Upon cooling to ambient temperature triethylamine (0.138 mL, 1.0 mmol) and 1-methyl-piperazine (0.1 mL, 0.9 mmol) were added and the whole reaction mixture was stirred over night at 50° C. After evaporation of the solvent, the residue was taken up in water and extracted with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and the filtrate was evaporated. The residue was taken up in a small amount of ethyl acetate, sonicated and kept over night in a refrigerator whereby a crystalline precipitate formed. The precipitate was isolated and dried on vacuum to yield the title compound (190 mg; 52%) as an off-white solid; MS: m/e=402.6 (M+H+).

Workup

  1. additionwere added
  2. customthe whole reaction mixture
  3. customAfter evaporation of the solvent
  4. extractionextracted with ethyl acetate
  5. customThe combined organic phases were dried on sodium sulfate
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customsonicated
  9. waitkept over night in a refrigerator whereby
  10. customa crystalline precipitate formed
  11. customThe precipitate was isolated
  12. customdried on vacuum

Sources & evidence

ORD record
ord-23f348de158e452a97caf0523d661d98
Source dataset
uspto-grants-2012_05
Patent number
US08183380B2

Reaction notes

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