1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 54579915, compound

HRID 1853971Notes

Reaction equation

HRID 1853971 reaction equation
[F:1][C:2]([F:10])([F:9])[CH2:3][CH2:4][CH2:5][C:6]([OH:8])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[S:42]1[CH:46]=[CH:45][N:44]=[C:43]1[C:47]1[N:51]=[C:50]([CH:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)[O:49][N:48]=1>CN(C=O)C>[F:9][C:2]([F:1])([F:10])[CH2:3][CH2:4][CH2:5][C:6]([N:55]1[CH2:54][CH2:53][CH:52]([C:50]2[O:49][N:48]=[C:47]([C:43]3[S:42][CH:46]=[CH:45][N:44]=3)[N:51]=2)[CH2:57][CH2:56]1)=[O:8]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27824465,5,5-trifluoropentanoic AcidHCID 89525386HCID 89525386, compound

Product 1

HCID 54579915HCID 54579915, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

5,5,5-Trifluoropentanoic acid (1.3 equiv), EDCI (1.3 equiv), HOBt (0.3 equiv) and DIEA (4 equiv) were mixed in DMF (40 mL) for 5 minutes. 4-(3-thiazol-2-yl-[1,2,4]oxadiazol-5-yl)-piperidine hydrochloride (5c) (8.18 g, 30 mmol, 1 equiv) was added with 20 mL of DMF and the reaction mixture was stirred overnight at room temperature and then evaporated under reduced pressure. The residue was dissolved in AcOEt and then washed twice with saturated aqueous NaHCO3, twice with HCl 1N and once with brine, then dried over MgSO4 and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (DCM/MeOH 100-0 to 98.5-1.5) and then recrystallized in a mixture of isopropanol and diisopropyl ether. Yield 62%; 1H NMR (CD2Cl2) δ 8.06 (d, J=3.0 Hz, 1H), 7.65 (d, J=3.0 Hz, 1H), 4.51-4.55 (m, 1H), 3.90-3.95 (m, 1H), 3.22-3.39 (m, 2H), 2.91-2.98 (m, 1H), 2.44 (t, J=7.2 Hz, 2H), 2.15-2.27 (m, 4H), 1.83-2.01 (m, 4H); 13C NMR (CDCl3) δ 182.06, 169.56, 163.97, 154.00, 144.95, 127.37 (q, J=275 Hz), 122.66, 44.33, 40.60, 34.43, 32.97 (q, J=29 Hz), 31.34, 29.44, 28.90, 17.52. mp 75.6-76.3° C.; tR LCMS 6.1 min. Purity >99%; MS [M+H]+ m/z 375.

Workup

  1. customevaporated under reduced pressure
  2. dissolutionThe residue was dissolved in AcOEt
  3. washwashed twice with saturated aqueous NaHCO3, twice with HCl 1N and once with brine
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (DCM/MeOH 100-0 to 98.5-1.5)
  7. customrecrystallized in a mixture of isopropanol and diisopropyl ether
  8. customtR LCMS 6.1 min

Sources & evidence

ORD record
ord-214a855b0e694d2ba4a26b83c0996b45
Source dataset
uspto-grants-2015_02
Patent number
US08962658B2

Reaction notes

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