Triethylamine → tert-Butyl 3-(4-(2-(4-Chloro-5-iodo-2-methoxyphenylamino)acetyl)piperazin-1-yl)azetidine-1-carboxylate

HRID 588854Notes

Reaction equation

HRID 588854 reaction equation
[Cl:1][C:2]1[C:7]([I:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([OH:13])=O)=[C:4]([O:14][CH3:15])[CH:3]=1.[N:16]1([CH:22]2[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[C:7]([I:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([N:19]2[CH2:20][CH2:21][N:16]([CH:22]3[CH2:23][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25]3)[CH2:17][CH2:18]2)=[O:13])=[C:4]([O:14][CH3:15])[CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 19360775tert-Butyl 3-(piperazin-1-yl)azetidine-1-carboxylateHCID 92135553N-(4-Chloro-5-iodo-2-methoxyphenyl)glycine

Product 1

HCID 90455712tert-Butyl 3-(4-(2-(4-Chloro-5-iodo-2-methoxyphenylamino)acetyl)piperazin-1-yl)azetidine-1-carboxylateYield 67.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-chloro-5-iodo-2-methoxyphenylamino)acetic acid (2.0 g, 5.88 mmol), tert-butyl 3-(piperazin-1-yl)azetidine-1-carboxylate (1.84 g, 7.64 mmol), EDCI.HCl (2.26 g, 11.76 mmol), and HOBt (1.59 g, 11.76 mmol) in DMF (3 mL) at 0° C., Et3N (3.28 mL, 23.52 mmol) was added. The resulting mixture was stirred at RT for 16 h and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was washed by a mixture of ethyl acetate/petroleum ether=1:5 to afford the desired product (2.24 g, 67% yield) as a white solid. ESI-MS m/z: 565.4[M+H]+.

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. washThe residue was washed by a mixture of ethyl acetate/petroleum ether=1:5

Sources & evidence

ORD record
ord-6998a0228f084809a593bf9aa04e22d1
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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