1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86611047, compound

HRID 1172354Notes

Reaction equation

HRID 1172354 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C:13]([C:15](O)=[O:16])=[CH:12][CH2:11][C@@H:10]1[C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[F:58][C:59]([F:70])([F:69])[C:60]1[N:61]=[C:62]2[CH2:67][NH:66][CH2:65][CH2:64][N:63]2[CH:68]=1>C1COCC1.CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[C@@H:10]([C:18]2[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=2[F:26])[CH2:11][CH:12]=[C:13]([C:15]([N:66]2[CH2:65][CH2:64][N:63]3[CH:68]=[C:60]([C:59]([F:70])([F:58])[F:69])[N:61]=[C:62]3[CH2:67]2)=[O:16])[CH2:14]1)([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11974549HCID 11974549, compoundHCID 441182832-(Trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine--hydrogen chloride (1/1)

Product 1

HCID 86611047HCID 86611047, compoundYield 106.5%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(4R,5S)-5-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-cyclohex-1-enecarboxylic acid (98.4 g) and EDCI (60.8 g 0.32 mol), HOBT (43 g, 0.32 mol) were mixed in THF/DMF (120 mL/120 mL). The mixture was cooled to 0° C. and diisopropylethyl amine (151.5 mL, 0.86 mol) was added slowly. The mixture was stirred for approximate twenty minutes, and then 2-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazine HCl salt (83.9 g, 0.32 mol) was added. The mixture was stirred overnight, and concentrated in vacuo. Ethyl acetate (1000 mL) was added followed by 1N HCl (750 mL). The mixture was extracted with ethyl acetate, and the combined organic extract was washed with saturated NaHCO3 (750 mL), water, and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give an oil (153.6 g). The crude amide (228 g) was dissolved in 470 mL of EtOH, and 1350 mL of hexanes was added with stirring. After stirring overnight, the solid was collected by filtration, washed with 450 mL of 50% Et2O/hexanes and then dried in vacuum at 45° C. to give 165.8 g (73%) of product as a white solid.

Workup

  1. stirringThe mixture was stirred overnight
  2. concentrationconcentrated in vacuo
  3. additionEthyl acetate (1000 mL) was added
  4. extractionThe mixture was extracted with ethyl acetate
  5. extractionthe combined organic extract
  6. washwas washed with saturated NaHCO3 (750 mL), water, and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-45891e3207454e078781b7a65854df9d
Source dataset
uspto-grants-2010_11
Patent number
US07834012B2

Reaction notes

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