1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59321391, compound

HRID 1800835Notes

Reaction equation

HRID 1800835 reaction equation
[F:1][C:2]1[C:3]([C:22]([OH:24])=O)=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1.[NH2:25][CH2:26][C:27]1([C:40]2[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=2)[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[F:1][C:2]1[C:3]([C:22]([NH:25][CH2:26][C:27]2([C:40]3[CH:41]=[CH:42][N:43]=[CH:44][CH:45]=3)[CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:31][CH2:32]2)=[O:24])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][N:16]=2)=[N:11][CH:10]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 592003973-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinic acid2×HCID 59321354HCID 59321354, compound

Product 1

HCID 59321391HCID 59321391, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-Fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinic acid (intermediate B in example 1, 612 mg, 1.7 mmol), tert-butyl 4-(aminomethyl)-4-(pyridin-4-yl)piperidine-1-carboxylate (amine intermediate “L”, 640 mg, 2.2 mmol), EDAC (649 mg, 3.4 mmol), HOBt (297 mg, 2.8 mmol) and diisopropyl-ethyl-amine (1.47 ml, 8.4 mmol) were dissolved in 15 ml NMP and stirred until LCMS showed complete consumption of acid starting material. (usually overnight) The product was precipitated out of the reaction mixture by addition of water, filtered, rinsed with water and dried. The title compound was isolated as a solid (1.01 g, 90% pure by HPLC, 83% yield). An analytical sample was purified by prep HPLC (C-18 reversed phase column, water/MeOH gradient, buffered with 0.1% TFA). Alternatively a water/acetonitrile gradient, buffered with 10 mM NH4OAc can be used. Product containing fractions were filtered through a cartridge filled with cation exchange resin (MCX from Waters or STRATA X-C from Phenomenex), rinsed with methanol, eluted with 2 M solution of ammonia in methanol and evaporated. The residue was dissolved in methanol, 1.0 equiv. aq. of 1.00 N HCl were added and the title compound was isolated as the mono-HCl salt by evaporation. LC/MS (M+H)+: 636. Ret. time: 1.66 min. (Condition M); analytical HPLC Ret. time: 16.74 min (Condition N).

Workup

  1. customconsumption of acid
  2. custom(usually overnight) The product was precipitated out of the reaction mixture by addition of water
  3. filtrationfiltered
  4. washrinsed with water
  5. customdried

Sources & evidence

ORD record
ord-39754fcf79144271bbde063eb30f903c
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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