N,N'-Dimethylethylenediamine → (+/-)-(E)-2-(7-chloro-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamide

HRID 390149Notes

Reaction equation

HRID 390149 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:29]=1[C:9]1([CH2:14][CH2:13][N:12]([C:15](=[O:28])/[CH:16]=[CH:17]/[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[CH2:11][CH2:10]1)[CH2:8][CH:7]2[CH2:30][C:31]([OH:33])=O.[CH3:34][NH:35][CH2:36][CH2:37][NH:38][CH3:39].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[ClH:70]>C(Cl)Cl>[Cl:70][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:29]=1[C:9]1([CH2:14][CH2:13][N:12]([C:15](=[O:28])/[CH:16]=[CH:17]/[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[CH2:11][CH2:10]1)[CH2:8][CH:7]2[CH2:30][C:31]([N:35]([CH3:34])[CH2:36][CH2:37][NH:38][CH3:39])=[O:33]

Participants

7

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58295679(+/-)-(E)-2-(7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetic acid

Product 1

HCID 44226675(+/-)-(E)-2-(7-chloro-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamideYield 18.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A vial was charged with (±)-(E)-2-(7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetic acid (5 mg, 0.01 mmol), N,N′-dimethylethylenediamine (0.007 mL, 0.066 mmol), HOBt (3 mg, 0.02 mmol), i-Pr2NEt (0.006 mL, 0.032 mmol) and CH2Cl2 (1 mL). EDC.HCl (4 mg, 0.021 mmol) was added. The mixture was stirred at rt for 1 d and evaporated to dryness. The residue was purified by preparative HPLC to afford (±)-(E)-2-(7-chloro-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)-N-methyl-N-(2-(methylamino)ethyl)acetamide (1.0 mg, 14%). LC-MS Method 1 tR=1.55, min, m/z=548, 550.

Workup

  1. customevaporated to dryness
  2. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-5b7719cb6d3344a0a38763a20bf533e5
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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