1-Chloro-N,N-2-trimethylpropenylamine → 4-{[1-(2-Benzo[b]thiophen-3-yl-acetyl)-2-methyl-azetidine-2-carbonyl]-benzofuran-6-ylmethyl-amino}-butyric acid ethyl ester

HRID 408600Notes

Reaction equation

HRID 408600 reaction equation
ClC(N(C)C)=C(C)C.[S:9]1[CH:13]=[C:12]([CH2:14][C:15]([N:17]2[CH2:20][CH2:19][C:18]2([CH3:24])[C:21]([OH:23])=O)=[O:16])[C:11]2[CH:25]=[CH:26][CH:27]=[CH:28][C:10]1=2.[CH2:29]([O:31][C:32](=[O:47])[CH2:33][CH2:34][CH2:35][NH:36][CH2:37][C:38]1[CH:46]=[CH:45][C:41]2[CH:42]=[CH:43][O:44][C:40]=2[CH:39]=1)[CH3:30]>C(Cl)Cl>[CH2:29]([O:31][C:32](=[O:47])[CH2:33][CH2:34][CH2:35][N:36]([C:21]([C:18]1([CH3:24])[CH2:19][CH2:20][N:17]1[C:15](=[O:16])[CH2:14][C:12]1[C:11]2[CH:25]=[CH:26][CH:27]=[CH:28][C:10]=2[S:9][CH:13]=1)=[O:23])[CH2:37][C:38]1[CH:46]=[CH:45][C:41]2[CH:42]=[CH:43][O:44][C:40]=2[CH:39]=1)[CH3:30]

Participants

5

Reactant 3

HCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 705564744-[(Benzofuran-6-ylmethyl)-amino]-butyric acid ethyl esterHCID 705573691-(2-Benzo[b]thiophen-3-yl-acetyl)-2-methyl-azetidine-2-carboxylic acid

Product 1

HCID 705567244-{[1-(2-Benzo[b]thiophen-3-yl-acetyl)-2-methyl-azetidine-2-carbonyl]-benzofuran-6-ylmethyl-amino}-butyric acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
20 °C

Procedure

To a solution of 1-chloro-N,N,2-trimethylpropenylamine (2 eq.) in DCM under nitrogen was added 1-(2-benzo[b]thiophen-3-yl-acetyl)-2-methyl-azetidine-2-carboxylic acid, Intermediate 121 (1 eq.). The solution was stirred at 20° C. for 1 h, then added to a solution of 4-[(Benzofuran-6-ylmethyl)-amino]-butyric acid ethyl ester, Intermediate 82 (1.2 eq.) in DCM at 0° C. TEA (2 eq.) was then added and the mixture was stirred at 0° C. for 3 h. The crude was diluted with DCM, washed twice with a saturated aqueous solution of NaHCO3, twice with aqueous HCl (0.5N), twice with water, dried over MgSO4, filtered, concentrated under reduced pressure and purified by chromatography on silica gel (elution with heptane/EtOAc 25/75 to 10/90) to afford 4-{[1-(2-benzo[b]thiophen-3-yl-acetyl)-2-methyl-azetidine-2-carbonyl]-benzofuran-6-ylmethyl-amino}-butyric acid ethyl ester.

Workup

  1. stirringthe mixture was stirred at 0° C. for 3 h
  2. washwashed twice with a saturated aqueous solution of NaHCO3, twice with aqueous HCl (0.5N), twice with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography on silica gel (elution with heptane/EtOAc 25/75 to 10/90)

Sources & evidence

ORD record
ord-cb53c0c3503e4d12bdb28cf05cf43ffb
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Reaction notes

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