3,5-Dichlorobenzoic acid → HCID 68981086, compound

HRID 749408Notes

Reaction equation

HRID 749408 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C@H:10]([CH2:14][CH2:15][N:16]2[CH2:19][CH:18]([N:20]3[CH2:25][CH2:24][S:23][CH2:22][CH2:21]3)[CH2:17]2)[CH2:11][NH:12][CH3:13])[CH:6]=[CH:7][C:8]=1[Cl:9].[Cl:26][C:27]1[CH:28]=[C:29]([CH:33]=[C:34]([Cl:36])[CH:35]=1)[C:30]([OH:32])=[O:31].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[C:30]([O-:32])(=[O:31])[CH3:29].[NH4+:12].[C:30]([OH:32])(=[O:31])[CH3:29].[Cl:36][C:34]1[CH:33]=[C:29]([CH:28]=[C:27]([Cl:26])[CH:35]=1)[C:30]([N:12]([CH2:11][C@H:10]([C:5]1[CH:6]=[CH:7][C:8]([Cl:9])=[C:3]([Cl:2])[CH:4]=1)[CH2:14][CH2:15][N:16]1[CH2:17][CH:18]([N:20]2[CH2:25][CH2:24][S:23][CH2:22][CH2:21]2)[CH2:19]1)[CH3:13])=[O:32]

Participants

9

Reactant 5

HCID 58113,5-Dichlorobenzoic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68977842HCID 68977842, compound

Product 2

HCID 517165Ammonium AcetateHCID 68981086HCID 68981086, compoundYield 90.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

[(2S)-2-(3,4-Dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylamine hydrochloride (see Method 1; 89 mg, 0.21 mmol) was dissolved in DMF (2 mL) and to the resultant solution were added 3,5-dichlorobenzoic acid (44 mg, 0.23 mmol), TBTU (80 mg, 0.25 mmol) and DIPEA (108 mg, 0.84 mmol) in the given order. The solution was stirred at room temperature for 1.5 h, diluted with water and then neutralized by the addition of NaHCO3. The mixture was extracted twice with ethyl acetate and the combined organic solutions were dried over MgSO4. The solvent was removed by evaporation to yield 79 mg of crude product. The product was purified by reversed phase chromatography using a mixture of acetonitrile and 0.1 M ammonium acetate aq. There was obtained 43 mg (37%) of the title compound as a white solid. 1 H NMR (500 MHz, CD3CN): 1.3-1.8 (cm, 3H), 2.0-4.6 (cm, 23H), 6.8-7.7 (cm, 5H), 8.0 (d, 1H); LCMS: m/z 560 (M+1)+.

Workup

  1. extractionThe mixture was extracted twice with ethyl acetate
  2. dry with materialthe combined organic solutions were dried over MgSO4
  3. customThe solvent was removed by evaporation
  4. customto yield 79 mg of crude product
  5. customThe product was purified by reversed phase chromatography
  6. additiona mixture of acetonitrile

Sources & evidence

ORD record
ord-7c42d5e3841a4dccaa4eb63716e600e4
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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