Diisopropylethylamine → HCID 89962080, compound

HRID 877431Notes

Reaction equation

HRID 877431 reaction equation
[CH3:1][C:2]1([CH3:18])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[O:3]1.Cl.[F:20][C:21]1([F:25])[CH2:24][NH:23][CH2:22]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[F:20][C:21]1([F:25])[CH2:24][N:23]([C:13]([C:12]2[CH:11]=[CH:10][C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:1])([CH3:18])[O:3]3)=[CH:17][CH:16]=2)=[O:15])[CH2:22]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27346214-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 89962080HCID 89962080, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (490 mg, 2.0 mmol), 3,3-difluoroazetidine hydrochloride (260 mg, 2.00 mmol), DIPEA (0.686 mL, 3.93 mmol) and HATU (900 mg, 2.4 mmol) in DMF (4 mL) was stirred at room temperature for 3 days. The reaction mixture was diluted with EtOAc, the organic portion washed successively with water and brine, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting with 0-100% EtOAc/hexane) to give Compound B166a (360 mg, 57% yield) as a white solid. HPLC: RT=1.9 min (LCMS Method Q). MS (ES): m/z=324.0 [M+H]+. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.87 (s, 2H), 7.62 (d, J=8.1 Hz, 2H), 4.53 (t, J=12.0 Hz, 4H), 1.36 (s, 12H).

Workup

  1. washthe organic portion washed successively with water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (eluting with 0-100% EtOAc/hexane)
  6. customto give Compound B166a (360 mg, 57% yield) as a white solid

Sources & evidence

ORD record
ord-17368f82cfd347b28983392b5e6e5984
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

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