4-Chlorobenzoic Acid → HCID 57345427, compound

HRID 1808848Notes

Reaction equation

HRID 1808848 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:42]1([C@@H:46]([NH:53][CH3:54])[CH2:47][N:48]2[CH2:51][CH:50]([OH:52])[CH2:49]2)[CH2:45][CH2:44][CH2:43]1>C(Cl)Cl.CN1C(=O)CCC1>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([N:53]([C@H:46]([CH:42]2[CH2:45][CH2:44][CH2:43]2)[CH2:47][N:48]2[CH2:49][CH:50]([OH:52])[CH2:51]2)[CH3:54])=[O:17])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 63184-Chlorobenzoic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67774176HCID 67774176, compound

Product 1

HCID 57345427HCID 57345427, compoundYield 52.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

DIPEA (0.275 mL, 1.57 mmol) was added to a suspension of 4-chlorobenzoic acid (82 mg, 0.52 mmol) and TBTU (168 mg, 0.52 mmol) in DCM (1 mL) at rt. The reaction mixture was stirred for 45 min before a solution of (R)-1-(2-cyclobutyl-2-(methylamino)ethyl)azetidin-3-ol (Compound G2.6) (184 mg, 0.52 mmol) in NMP (1.000 mL) was added. The reaction mixture was stirred at rt over the weekend. The reaction mixture was washed with NaHCO3 (8% aq.2 mL). The organic layer was passed through a phase separator and the solvent was removed in vacuo. The residue was purified by preparative HPLC to give the title compound (88 mg, 52%). 1H NMR (600 MHz, DMSO-d6) δ 1.38-1.52, 1.55-1.62, 1.64-1.95, 2.00-2.06, 2.21-2.25, 2.27-2.33, 2.36-2.43, 2.55-2.62, 2.64-2.68, 2.70-2.72, 2.73-2.79, 3.23-3.26, 3.40-3.44, 3.54-3.57, 4.11-4.18, 4.43-4.51, 5.20-5.27, 7.29-7.35, 7.47-7.54. HRMS (M+H)+: calculated 323.1526. found 323.1535

Workup

  1. additionwas added
  2. washThe reaction mixture was washed with NaHCO3 (8% aq.2 mL)
  3. customthe solvent was removed in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-70811c483f984cc2ae59870ba46031b2
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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