4-Cyanobenzoic acid → HCID 57345440, compound

HRID 1808853Notes

Reaction equation

HRID 1808853 reaction equation
CCN(C(C)C)C(C)C.[C:10]([C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=1)#[N:11].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:43]1([C@H:47]([NH:54][CH3:55])[CH2:48][N:49]2[CH2:52][CH:51]([OH:53])[CH2:50]2)[CH2:46][CH2:45][CH2:44]1>C(Cl)Cl>[C:10]([C:12]1[CH:13]=[CH:14][C:15]([C:16]([N:54]([C@@H:47]([CH:43]2[CH2:46][CH2:45][CH2:44]2)[CH2:48][N:49]2[CH2:50][CH:51]([OH:53])[CH2:52]2)[CH3:55])=[O:18])=[CH:19][CH:20]=1)#[N:11]

Participants

6

Reactant 4

HCID 120874-Cyanobenzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67772265HCID 67772265, compound

Product 1

HCID 57345440HCID 57345440, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIPEA (2.504 mL, 14.38 mmol) was added to a stirred suspension of 4-cyanobenzoic acid (0.670 g, 4.55 mmol) and TBTU (1.462 g, 4.55 mmol) in DCM (10 mL) at rt. The suspension was stirred for 5 min before it was cooled on an ice-bath. A solution of (S)-1-(2-cyclobutyl-2-(methylamino)ethyl)azetidin-3-ol (Compound Z2.1) (0.960 g, 4.79 mmol) in DCM (10 mL) was added over 5 min. The ice-bath was removed after 10 min and the reaction was stirred at rt for 3 h. The reaction mixture was diluted with DCM (20 mL), washed with NaHCO3 (8% aq., 35 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The selected fractions were concentrated and NaHCO3 (saturated, 40 mL) was added. The water layer was extracted with DCM (3×75 mL) and the combined organic layers were filtered through a phase separator and concentrated under reduced pressure to give the title compound (0.925 g, 62%). Mixture of rotamers: 1H NMR (400 MHz, DMSO-d6) δ 1.32-1.62, 1.65-1.97, 1.97-2.08, 2.17-2.28, 2.32-2.60, 2.62-2.74, 3.16-3.27, 3.39-3.45, 3.46-3.52, 4.07-4.18, 4.40-4.52, 5.19-5.24, 7.42-7.46, 7.57-7.62, 7.87-7.95.

Workup

  1. temperaturewas cooled on an ice-bath
  2. customThe ice-bath was removed after 10 min
  3. stirringthe reaction was stirred at rt for 3 h
  4. additionThe reaction mixture was diluted with DCM (20 mL)
  5. washwashed with NaHCO3 (8% aq., 35 mL)
  6. filtrationfiltered through a phase separator
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC
  9. concentrationThe selected fractions were concentrated
  10. additionNaHCO3 (saturated, 40 mL) was added
  11. extractionThe water layer was extracted with DCM (3×75 mL)
  12. filtrationthe combined organic layers were filtered through a phase separator
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-93316eff071b413da34e71a51c659254
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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