Dimethylamine → HCID 66549429, compound

HRID 2174391Notes

Reaction equation

HRID 2174391 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[N:26]1[CH2:29][CH:28]([C:30](O)=[O:31])[CH2:27]1.[CH3:33][N:34](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:35].F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CNC>CN(C=O)C.C1COCC1>[CH3:33][N:34]([CH3:35])[C:30]([CH:28]1[CH2:27][N:26]([C:3]2[CH:4]=[CH:5][C:6]([C:8]3[CH2:12][C:11]([C:17]4[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=4)([C:13]([F:16])([F:14])[F:15])[O:10][N:9]=3)=[CH:7][C:2]=2[Cl:1])[CH2:29]1)=[O:31]

Participants

7

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86707798HCID 86707798, compound

Product 1

HCID 66549429HCID 66549429, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1-{2-Chloro-4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-azetidine-3-carboxylic acid (Preparation 14, 0.1 g, 0.189 mmol) in dry DMF (1 mL) was added HATU (0.108 g, 0.284 mmol) HOBt (0.028 g, 0.207 mmol), DIPEA (0.048 g, 0.378 mmol) and saturated solution of dimethyl amine in THF (2 mL) at 0° C. and stirred at 0° C. for 2 hours and at room temperature for 18 hours. After complete consumption of starting material, reaction mixture was quenched with water (15 mL), extracted with EtOAc (10 mL). Organic layer was washed with saturated solution of lithium chloride (2×20 mL), water (2×20 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). Further purification by preparative TLC using 5% MeOH in DCM afforded white solid (0.020 g, 19%). 1H-NMR (400 MHz, CDCl3) δ: 2.95 (s, 3H), 2.97 (s, 3H), 3.59 (d, 1H, J=17.08 Hz), 3.67-3.71 (m, 1H), 4.00 (d, 1H, J=17.04 Hz), 4.29-4.38 (m, 4H), 6.48 (d, 1H, J=8.6 Hz), 7.40 (dd, 1H, J1=8.48 Hz, J2=2 Hz), 7.45 (d, 1H, J=1.92 Hz), 7.62 (s, 2H); LC-MS (m/z): [M+H] 554.10.

Workup

  1. customAfter complete consumption of starting material, reaction mixture
  2. customwas quenched with water (15 mL)
  3. extractionextracted with EtOAc (10 mL)
  4. washOrganic layer was washed with saturated solution of lithium chloride (2×20 mL), water (2×20 mL)
  5. dry with materialdried over sodium sulphate
  6. customevaporated in vacuo
  7. customto get crude
  8. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  9. customFurther purification by preparative TLC

Sources & evidence

ORD record
ord-d6966cf8521e4402900ee951eb982d93
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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