Diisopropylethylamine → HCID 53349361, compound

HRID 2357065Notes

Reaction equation

HRID 2357065 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@:12]([CH3:16])([C:13]([OH:15])=O)[CH2:11][O:10][C:9]1([CH3:18])[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH2:52]([O:60][C:61]1[CH:70]=[CH:69][C:64]([C:65]([NH:67][NH2:68])=[O:66])=[CH:63][C:62]=1[C:71]([F:74])([F:73])[F:72])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59]>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[CH3:17][C:9]1([CH3:18])[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@:12]([CH3:16])([C:13]([NH:68][NH:67][C:65](=[O:66])[C:64]2[CH:69]=[CH:70][C:61]([O:60][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])=[C:62]([C:71]([F:72])([F:74])[F:73])[CH:63]=2)=[O:15])[CH2:11][O:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 52987736HCID 52987736, compoundHCID 533493604-(Octyloxy)-3-(trifluoromethyl)benzohydrazide

Product 1

HCID 53349361HCID 53349361, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

(R)-3-(tert-Butoxycarbonyl)-2,2,4-trimethyloxazolidine-4-carboxylic acid (4) (210 mg, 0.81 mmol) was stirred with HATU (372 mg, 0.98 mmol) and diisopropylethyl amine (DIEA) (0.705 mL, 4.1 mmol) in CH2Cl2-DMF (2:1, 6 mL) for 10 min followed by addition of 4-(octyloxy)-3-(trifluoromethyl)benzohydrazide (12a) (270 mg, 0.81 mmol) in CH2Cl2 (2 mL). The reaction was stirred at room temperature for 1 hour and then was concentrated under vacuum. The residue was diluted with ethyl acetate (20 mL) and washed with water (5 mL), brine (2×10 mL) and dried over Na2SO4. The organic layer was concentrated in vacuo and chromatographed on a silica gel column (ethyl acetate-hexane, 0-33%, as eluent) to afford the title compound (428 mg, 82% yield). MS (ESI): 573.84 (MH+); 1H NMR (400 MHz, CDCl3) δ 9.43 (br, 2H), 8.06 (d, 1H, J=2.0 Hz), 7.94 (dd, 1H, J=8.8 Hz, J=2.0 Hz), 6.96 (d, 1H, J=8.8 Hz), 4.52 (br, 1H), 4.07 (t, 2H, J=6.4 Hz), 3.76 (br, 1H), 1.82 (m, 2H), 1.67 (s, 6H), 1.57 (s, 3H), 1.51 (s, 9H), 1.51-1.43 (m, 4H), 1.38-1.24 (m, 6H), 0.88 (t, 3H, J=7.2 Hz).

Workup

  1. concentrationwas concentrated under vacuum
  2. additionThe residue was diluted with ethyl acetate (20 mL)
  3. washwashed with water (5 mL), brine (2×10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationThe organic layer was concentrated in vacuo
  6. customchromatographed on a silica gel column (ethyl acetate-hexane, 0-33%, as eluent)

Sources & evidence

ORD record
ord-8dbe47df46924acc83a2c7f777bd05b5
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

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