Dimethylamine → HCID 66548858, compound

HRID 2174367Notes

Reaction equation

HRID 2174367 reaction equation
[OH: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.[CH3:33][N:34](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:35].F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CNC>CN(C=O)C.C1COCC1>[CH3:33][N:34]([CH3:35])[C:6]([CH:4]1[CH2:3][C:2]([OH:1])([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:25]=[C:26]([Cl:32])[C:27]([Cl:31])=[C:28]([Cl:30])[CH:29]=4)([C:20]([F:23])([F:22])[F:21])[O:17][N:16]=3)=[CH:13][CH:14]=2)[CH2:5]1)=[O:8]

Participants

8

Reactant 5

HCID 674DimethylamineHCID 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 86707791HCID 86707791, compound

Product 1

HCID 66548858HCID 66548858, compoundYield 55.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (Preparation 4, 0.050 g, 0.098 mmol) in dry DMF (1 mL) was added HATU (0.056 g, 0.147 mmol), HOBt (0.014 g, 0.107 mmol), DIPEA (0.025 g, 0.196 mmol) and saturated solution of dimethyl amine in THF (2 mL) at 0° C. Resulting reaction mixture was stirred 0° C. for 1 hour and at room temperature for 18 hours. After complete consumption of starting material, reaction mixture was quenched with water (5 mL), extracted with EtOAc (10 mL). Organic layer was washed with saturated solution of lithium chloride (2×20 mL), brine (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 1.2% methanol in DCM to afford sticky mass, which was crystallized by chloroform:pentane (1:9) to afford white solid (0.029 g, 55%). 1H-NMR (400 MHz, CDCl3) δ: 2.53-2.57 (m, 2H), 2.79-2.88 (m, 2H), 3.02 (s, 6H), 3.27-3.31 (m, 1H), 3.67 (d, 1H, J=17.2 Hz), 4.08 (d, 1H, J=17.16 Hz), 5.04 (s, 1H), 7.57 (d, 2H, J=8.4 Hz), 7.64-7.65 (m, 4H); LC-MS (m/z): [M+H] 534.8.

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. customwas quenched with water (5 mL)
  5. extractionextracted with EtOAc (10 mL)
  6. washOrganic layer was washed with saturated solution of lithium chloride (2×20 mL), brine (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
  12. customto afford sticky mass, which
  13. customwas crystallized by chloroform:pentane (1:9)

Sources & evidence

ORD record
ord-fe894b0e8fe04e71b6c2d59e238c7bb2
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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