Propanal → 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-4'-((propylamino)methyl)biphenyl-3-yl)cyclopropanecarboxamide

HRID 83734Notes

Reaction equation

HRID 83734 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]([CH3:15])=[CH:13][CH:12]=[C:11]([NH:16][C:17]([C:19]3([C:22]4[CH:30]=[CH:29][C:25]5[O:26][CH2:27][O:28][C:24]=5[CH:23]=4)[CH2:21][CH2:20]3)=[O:18])[CH:10]=2)=[CH:5][CH:4]=1.[CH:31](=O)[CH2:32][CH3:33].[BH4-].[Na+]>ClCCl.COCCOC.O>[O:26]1[C:25]2[CH:29]=[CH:30][C:22]([C:19]3([C:17]([NH:16][C:11]4[CH:10]=[C:9]([C:6]5[CH:5]=[CH:4][C:3]([CH2:2][NH:1][CH2:31][CH2:32][CH3:33])=[CH:8][CH:7]=5)[C:14]([CH3:15])=[CH:13][CH:12]=4)=[O:18])[CH2:20][CH2:21]3)=[CH:23][C:24]=2[O:28][CH2:27]1

Participants

7

Reactant 3

HCID 527PropanalHCID 4311764Sodium borohydrideHCID 59205919N-(4'-(Aminomethyl)-6-methylbiphenyl-3-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Product 1

HCID 592059541-(benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-4'-((propylamino)methyl)biphenyl-3-yl)cyclopropanecarboxamideYield 17.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
25 °C

Procedure

N-(4′-(Aminomethyl)-6-methylbiphenyl-3-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (40 mg, 0.10 mmol), propionaldehyde (5.1 μL, 0.10 mmol) and Ti(OPr)4 (82 μL, 0.30 mmol) were dissolved in dichloromethane (1.0 mL) and mono-glyme (1.0 mL). The mixture was allowed to stir at 25° C. for 16 hours. NaBH4 (5.7 mg, 0.15 mmol) was added and the reaction was stirred for an additional 1 h. The reaction was diluted to 5 mL with dichloromethane before water (5 mL) was added. The reaction was filtered through celite to remove the titanium salts and the layers separated. The organic extracts were dried over Na2SO4 and evaporated. The crude product was purified by reverse phase HPLC to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-4′-((propylamino)methyl)biphenyl-3-yl)cyclopropanecarboxamide (7.8 mg, 14%). ESI-MS m/z calc. 442.6. found 443.5 (M+1)+; retention time 2.54 minutes.

Workup

  1. stirringthe reaction was stirred for an additional 1 h
  2. additionwas added
  3. filtrationThe reaction was filtered through celite
  4. customto remove the titanium salts
  5. customthe layers separated
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. customevaporated
  8. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-44d6f8b07c35488e88674f8524ac39b2
Source dataset
uspto-grants-2014_09
Patent number
US08846753B2

Reaction notes

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