Diisopropylethylamine → N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]-2-(4-pyrrolidin-1-ylphenyl)acetamide

HRID 254708Notes

Reaction equation

HRID 254708 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH2:27])[CH3:26])=[N:23][CH:24]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([C@H:25]([NH:27][C:13](=[O:15])[CH2:12][C:9]2[CH:8]=[CH:7][C:6]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:11][CH:10]=2)[CH3:26])=[N:23][CH:24]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 141545872-[4-(Pyrrolidin-1-yl)phenyl]acetic acidHCID 66892986(R)-1-(5-Methoxypyridin-2-yl)ethanamine hydrochloride

Product 1

HCID 24765480N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]-2-(4-pyrrolidin-1-ylphenyl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (4-pyrrolidin-1-ylphenyl)acetic acid (U.S. Pat. No. 3,641,040) (0.50 g, 2.4 mmol), (1R)-1-(5-methoxypyridin-2-yl)ethylamine hydrochloride (0.57 g, 3.0 mmol), and HATU (1.2 g, 3.1 mmol) in DMF (3 mL) was added N,N-diisopropylethylamine (1.7 mL, 9.7 mmol) and the mixture was stirred at room temperature for 16 h. The solution was concentrated and the crude residue was partitioned between water and EtOAc. The organic layer was washed with brine and water, dried over MgSO4, and purified by normal phase chromatography (10-100% EtOAc/hexanes) to give N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]-2-(4-pyrrolidin-1-ylphenyl)acetamide as a tan solid. 1H NMR (400 MHz, CDCl3) δ 8.16 (m, 1H), 7.11 (m, 4H), 6.54 (m, 3H), 5.09 (m, 1H), 3.83 (s, 3H), 3.48 (d, J=3.2 Hz, 2H), 3.28 (t, J=6.4 Hz, 4H), 2.01 (m, 4H), 1.36 (d, J=6.4 Hz, 3H); MS (Electrospray): m/z 340.4 (M+H)

Workup

  1. concentrationThe solution was concentrated
  2. customthe crude residue was partitioned between water and EtOAc
  3. washThe organic layer was washed with brine and water
  4. dry with materialdried over MgSO4
  5. custompurified by normal phase chromatography (10-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-84aecc52db5e4d2ea186e522bbc29c36
Source dataset
uspto-grants-2011_01
Patent number
US07875636B2

Reaction notes

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