Methylamine → HCID 66548857, compound

HRID 2174366Notes

Reaction equation

HRID 2174366 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)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CN>CN(C=O)C.C1COCC1>[CH3:33][NH:34][C:6]([CH:4]1[CH2:5][C:2]([OH: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:22])([F:23])[F:21])[O:17][N:16]=3)=[CH:13][CH:14]=2)[CH2:3]1)=[O:8]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 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 66548857HCID 66548857, compoundYield 29.2%

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, 0.060 g, 0.118 mmol) in dry DMF (1 mL) was added HATU (0.067 g, 0.177 mmol), HOBt (0.0175 g, 0.129 mmol), DIPEA (0.03 g, 0.236 mmol) and saturated solution of methyl amine in THF (2 mL) at 0° C. Resulting reaction mixture was stirred 0° C. for 2 hours 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), water (2×20 mL), dried over sodium sulphate and evaporated in vacuo to get brown 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 (0.018 g, 29%). 1H-NMR (400 MHz, CDCl3) δ: 2.49-2.52 (m, 2H), 2.81-2.83 (m, 2H), 2.84-2.86 (m, 1H), 2.88 (d, 3H, J=4.88 Hz), 3.67 (d, 1H, J=17.08 Hz), 4.07 (d, 1H, J=17.16 Hz), 5.67 (bs, 1H), 5.81 (s, 1H), 7.55 (d, 2H, J=8.4 Hz), 7.62-7.64 (m, 4H). LC-MS (m/z): [M−H] 518.80. HPLC purity: 98.48%.

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), water (2×20 mL)
  7. dry with materialdried over sodium sulphate
  8. customevaporated in vacuo
  9. customto get brown 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-7ca46cd8bf0441c28801bc5a40e383dd
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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