Diisopropylethylamine → HCID 67774106, compound

HRID 1808817Notes

Reaction equation

HRID 1808817 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[CH3:11].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[N:43]1([CH2:47][C@H:48]([CH:51]2[CH2:53][CH2:52]2)[NH:49][CH3:50])[CH2:46][CH2:45][CH2:44]1>C(Cl)Cl>[N:43]1([CH2:47][C@@H:48]([N:49]([CH3:50])[C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([F:1])=[C:3]([CH3:11])[CH:4]=2)[CH:51]2[CH2:53][CH2:52]2)[CH2:46][CH2:45][CH2:44]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2428284-Fluoro-3-methylbenzoic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67773433HCID 67773433, compound

Product 1

HCID 67774106HCID 67774106, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-fluoro-3-methylbenzoic acid (330 mg, 2.14 mmol) and DIPEA (0.508 mL, 2.92 mmol) in DCM (3 mL) was TBTU (687 mg, 2.14 mmol) added. After 10 min was a solution of (S)-2-(azetidin-1-yl)-1-cyclopropyl-N-methylethanamine (Compound L1) (300 mg, 1.94 mmol) in DCM (3 mL) added. The resultant mixture was stirred at r.t for 6 h. The mixture was washed with NaHCO3 (8% aq., 5 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (353 mg, 63%). Mixture of rotamers: 1H NMR (600 MHz, CD3OD) δ 0.04-0.14, 0.31-0.40, 0.40-0.48, 0.48-0.57, 0.59-0.66, 0.67-0.75, 0.92-1.06, 2.01-2.07, 2.07-2.16, 2.29, 2.30, 2.56-2.65, 2.76-2.88, 2.90, 2.94-3.00, 3.02, 3.09-3.21, 3.26-3.37, 3.80-3.91, 7.04-7.14, 7.22-7.40. Total no of protons: 23. HRMS (M+H)+: calculated 291.1873. found 291.1865.

Workup

  1. additionadded
  2. washThe mixture was washed with NaHCO3 (8% aq., 5 mL)
  3. filtrationfiltered through a phase separator
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-db22036d057145be8b5abd733c1e3487
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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