Ethylamine → HCID 66549045, compound

HRID 2174377Notes

Reaction equation

HRID 2174377 reaction equation
[F:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:29]=[C:28]([Cl:30])[C:27]([Cl:31])=[C:26]([Cl:32])[CH:25]=4)([C:20]([F:23])([F:22])[F:21])[O:17][N:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH:4]([C:6]([OH:8])=O)[CH2:3]1.CN(C(O[N:41]1N=N[C:43]2C=CC=N[C:42]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(N)C>CN(C=O)C.C1COCC1>[CH2:42]([NH:41][C:6]([CH:4]1[CH2:5][C:2]([F:1])([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:29]=[C:28]([Cl:30])[C:27]([Cl:31])=[C:26]([Cl:32])[CH:25]=4)([C:20]([F:21])([F:22])[F:23])[O:17][N:16]=3)=[CH:13][CH:14]=2)[CH2:3]1)=[O:8])[CH3:43]

Participants

8

Reactant 5

HCID 6341EthylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86707793HCID 86707793, compound

Product 1

HCID 66549045HCID 66549045, compoundYield 95.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-Fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (Preparation 6, 0.2 g, 0.391 mmol) in dry DMF (3 mL) was added HATU (0.223 g, 0.58 mmol), HOBt (0.06 g, 0.43 mmol), DIPEA (0.102 g, 0.79 mmol) and 2M solution of ethyl amine in THF (2 mL) at 0° C. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (20 mL), extracted with EtOAc (2×30 mL). Combined organic layer was washed with brine (2×20 mL), saturated solution of lithium chloride (2×20 mL), water (20 mL), dried over sodium sulphate and evaporated in vacuo to get crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 1% methanol in DCM to afford off white solid (0.20 g, 64%). 1H-NMR (400 MHz, CDCl3) δ: 1.15 (t, 3H, J=7.28 Hz), 2.67-2.78 (m, 2H), 2.84-2.96 (m, 2H), 3.22-3.26 (m, 1H), 3.28-3.35 (m, 2H), 3.67 (d, 1H, J=17.24 Hz), 4.07 (d, 1H, J=17.2 Hz), 5.43 (bs, 1H), 7.56 (d, 2H, J=8.36 Hz), 7.64-7.66 (m, 4H); LC-MS (m/z): [M−H] 535.00.

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. customwas quenched with water (20 mL)
  5. extractionextracted with EtOAc (2×30 mL)
  6. washCombined organic layer was washed with brine (2×20 mL), saturated solution of lithium chloride (2×20 mL), water (20 mL)
  7. dry with materialdried over sodium sulphate
  8. customevaporated in vacuo
  9. customto get crude
  10. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  11. washCompound was eluted

Sources & evidence

ORD record
ord-5bdf44284f6a48eab791d9d3e5b06599
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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