4-Fluorobenzoic Acid → HCID 68651671, compound

HRID 646774Notes

Reaction equation

HRID 646774 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]2)=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH2:15])[CH:9]=2)=[CH:6][N:7]=1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.O>[NH2:1][C:2]1[C:3]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]2)=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH:15][C:37]([C:36]3[CH:40]=[CH:41][C:33]([F:32])=[CH:34][CH:35]=3)=[O:38])[CH:9]=2)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 99734-Fluorobenzoic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 58710569HCID 58710569, compound

Product 1

HCID 68651671HCID 68651671, compoundYield 46.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1,1-dimethylethyl (3S)-3-[({3-amino-6-[3-(amino-methyl)phenyl]pyrazin-2-yl}carbonyl)amino]piperidine-1-carboxylate (150.0 mg, 0.35 mmol) and 4-fluorobenzoic acid (50.0 mg, 0.36 mmol) was dissolved in DMF (5 mL) followed by the addition of HOBT (95.5 mg, 0.70 mmol) and EDCI (135.4 mg, 0.70 mmol). It was stirred at room temperature overnight. The reaction mixture was poured into water (20 mL), and extracted with ethyl acetate (2×30 mL) then dried over anhydrous sodium sulfate and filteration, concentration and purified by column chromatography (50% Ethylacetae/hexanes) and subsequently it was treated with 4.0 M HCl in dioxane (20 mL) to give compound 3-Amino-6-[3-({[(4-fluorophenyl)carbonyl]amino}methyl)phenyl]-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide: 70.0 mg (46.6% yield). 1H NMR (400 MHz, d4-MeOH): δ 8.62 (s, 1H), 8.16 (s, 1H), 7.98 (m, 3H), 7.48 (m, 2H), 7.20 (m, 3H), 4.67(s, 2H), 4.38 (m, 1H), 3.45 (m, 1H), 3.38 (m, 1H), 3.18 (m, 1H), 3.00 (m, 1H), 2.18 (m, 2H), 1.80 (m, 2H); MS (EI) for C24H25N6O2F: 449.32 (MH+).

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. dry with materialthen dried over anhydrous sodium sulfate and filteration, concentration
  3. custompurified by column chromatography (50% Ethylacetae/hexanes) and subsequently it
  4. additionwas treated with 4.0 M HCl in dioxane (20 mL)

Sources & evidence

ORD record
ord-ff2f5cf0c1f54a0382d07a63abbd591f
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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