Diisopropylethylamine → HCID 58466410, compound

HRID 1874637Notes

Reaction equation

HRID 1874637 reaction equation
[CH3:1][CH:2]([CH2:21][CH2:22][CH3:23])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C@@H:11]([NH2:20])[CH2:12][N:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[CH:7][CH:6]=1.[CH:24](N(CC)C(C)C)([CH3:26])[CH3:25].CN(C(ON1N=N[C:43]2[CH:44]=[CH:45][CH:46]=N[C:42]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:57]([O-:60])(O)=O.[Na+]>ClCCl>[CH3:1][CH:2]([CH2:21][CH2:22][CH3:23])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([NH:20][C:57](=[O:60])[C@H:43]([C:44]2[CH:26]=[CH:24][CH:25]=[CH:46][CH:45]=2)[CH3:42])[CH2:12][N:13]2[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]2)=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67439336HCID 67439336, compound

Product 1

HCID 58466410HCID 58466410, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R)-1-(4-(2-methylpentyloxy)phenyl)-2-(4-methylpiperazin-1-yl)ethanamine.3TFA (79 mg, 0.119 mmol) in dichloromethane (2 mL) at room temperature was added N,N-diisopropylethylamine (0.125 mL, 0.717 mmol) followed by HATU (68.1 mg, 0.179 mmol). The mixture was stirred at room temperature under N2 overnight. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (50 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated. The product was purified by reverse phase HPLC (acetonitrile/water with 0.1% TFA). The organic solvent was removed on the rotovapor and the aqueous mixture was frozen and placed on the lyophilizer to afford (2S)-N-(1-(4-(2-methylpentyloxy)phenyl)-2-(4-methylpiperazin-1-yl)ethyl)-2-phenylpropanamide (41 mg, 61% yield) as a colorless amorphous solid. LC/MS and HPLC showed that the product is a 1:1 mixture of diastereomers. The total number of protons in the 1H NMR is doubled to account for presence of both diasteriomers: 1H NMR (400 MHz, DMSO-d6) δ 8.29 (t, J=8.4 Hz, 2H), 7.31-7.41 (m, 4H), 7.22-7.29 (m, 7H), 7.16-7.21 (m, 1H), 7.11 (d, 2H), 6.89 (d, J=8.6 Hz, 2H), 6.78 (d, 2H), 4.88-4.99 (m, 2H), 3.62-3.85 (m, 6H), 3.37 (br. s., 4H), 3.20 (br. s., 4H), 2.98 (br. s., 8H), 2.77 (s, 3H), 2.66 (s, 3H), 2.17-2.44 (m, 4H), 1.85 (td, J=13.0, 6.5 Hz, 2H), 1.36 (d, J=7.1 Hz, 3H), 1.29 (d, J=6.8 Hz, 3H), 1.23-1.46 (m, 6H), 1.11-1.22 (m, 2H), 0.96 (d, J=6.8 Hz, 3H), 0.93 (d, J=6.8 Hz, 3H), 0.89 (t, J=6.8 Hz, 3H), 0.87 (t, J=6.5 Hz, 3H); LRMS (ESI) m/e 452.3 [(M+H)+, calcd for C28H42N3O2 452.3].

Workup

  1. customThe reaction mixture was transferred to a separatory funnel
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by reverse phase HPLC (acetonitrile/water with 0.1% TFA)
  8. customThe organic solvent was removed on the rotovapor
  9. temperaturethe aqueous mixture was frozen

Sources & evidence

ORD record
ord-99ab1a6febd24d92acbd1d452ec56075
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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