Ethanamine, 2,2,2-trifluoro- → HCID 86722545, compound

HRID 1503540Notes

Reaction equation

HRID 1503540 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]([C:28]([F:31])([F:30])[F:29])/[CH:11]=[CH:12]/[C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[C:19](=[O:23])[N:18]([CH2:24][C:25]([OH:27])=O)[N:17]=[CH:16]3)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].[F:32][C:33]([F:37])([F:36])[CH2:34][NH2:35].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]([C:28]([F:29])([F:31])[F:30])/[CH:11]=[CH:12]/[C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[C:19](=[O:23])[N:18]([CH2:24][C:25]([NH:35][CH2:34][C:33]([F:37])([F:36])[F:32])=[O:27])[N:17]=[CH:16]3)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]

Participants

6

Reactant 4

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 86675175HCID 86675175, compound

Product 1

HCID 86722545HCID 86722545, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (E)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)acetic acid (0.15 g, 0.31 mmol) in DCM (20.0 ml) was added 2,2,2,-trifluoroethanamine (0.03 g, 0.31 mmol), PyBOP (0.17 g, 0.34 mmol) and DIEA (0.15 ml, 0.93 mmol) at RT, and the reaction was stirred for 18 h. The reaction mixture was diluted with DCM and washed with 3N HCl (2×20 mL), NaHCO3 (2×20 mL) and brine solution (2×). The separated DCM layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 20-25% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.11 g): mp 172-175° C.; 1H NMR (400 MHz, CDCl3) δ 8.83 (t, J=6.6 Hz, 1H), 8.42 (t, J=14.7 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.13 (t, J=6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H); ESIMS m/z 554.0 ([M−H]−).

Workup

  1. washwashed with 3N HCl (2×20 mL), NaHCO3 (2×20 mL) and brine solution (2×)
  2. dry with materialThe separated DCM layer was dried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto afford the crude compound
  5. customThe crude compound was purified by column chromatography (SiO2, 100-200 mesh; 20-25% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-c0751c0b432747ef98a5e3ad43490881
Source dataset
uspto-grants-2015_12
Patent number
US09212163B2

Reaction notes

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