Propanenitrile, 3-(methylamino)- → HCID 28387176, compound

HRID 1684861Notes

Reaction equation

HRID 1684861 reaction equation
CCN(C(C)C)C(C)C.[Br:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14]Br.[CH3:19][NH:20][CH2:21][CH2:22][C:23]#[N:24]>CN(C=O)C>[Br:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14][N:20]([CH3:19])[CH2:21][CH2:22][C:23]#[N:24]

Participants

5

Reactant 3

HCID 69656Propanenitrile, 3-(methylamino)-HCID 699793-Bromobenzyl bromideHCID 81531Diisopropylethylamine

Product 1

HCID 28387176HCID 28387176, compoundYield 116.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Hunig's base (26.5 mL, 0.15 mol) was added to 3-bromobenzyl bromide (38 g, 0.15 mol) and N-methyl-β-alanine nitrile (14.2 mL, 0.15 mol) in dry DMF (400 mL). The solution was stirred 16 h, concentrated in vacuo to near dryness, triturated with ether/EtOAc, and filtered. [A second reaction was repeated on 12 g]. The combined filtrates were concentrated by rotory evaporation and the residue was charged (CH2Cl2) to a 65 (M) Biotage® silica gel column; Segment 1: Gradient elution from 5-15% B over 1.3 L; Segment 2: 15%-100% B (A=Hexanes; B=EtOAc) over 6.75 L to give Example 4, 3-((3-bromobenzyl)(methyl)amino)-propanenitrile 44.4 g (88%). 1H NMR (500 MHz, DMSO-d6) δ 7.54 (s, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.34 (d, J=7.6 Hz, 1H), 7.30 (t, J=7.6 Hz, 1H), 3.54 (s, 2H), 2.71 (t, J=6.4 Hz, 2H), 2.63 (t, J=6.4 Hz, 2H), 2.17 (s, 3H). RT=1.1 minutes (condition 2); LRMS: Anal. Calcd. for C11H13BrN2: 253.03. found: 253.05 (M+H).

Workup

  1. concentrationconcentrated in vacuo
  2. customtriturated with ether/EtOAc
  3. filtrationfiltered
  4. custom[A second reaction
  5. concentrationThe combined filtrates were concentrated by rotory evaporation
  6. additionthe residue was charged (CH2Cl2) to a 65 (M) Biotage® silica gel column
  7. washSegment 1: Gradient elution from 5-15% B over 1.3 L

Sources & evidence

ORD record
ord-04fa279172924d3b96489824bf98d2aa
Source dataset
uspto-grants-2012_04
Patent number
US08147818B2

Reaction notes

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