Triethylamine → tert-Butyl (3-[cyclopropyl(pyridin-4-ylmethyl)amino]-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

HRID 561890Notes

Reaction equation

HRID 561890 reaction equation
[NH2:1][CH2:2][CH:3]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][O:31][C:32]2[C:37]([Cl:38])=[CH:36][C:35]([CH3:39])=[CH:34][C:33]=2[Cl:40])=[CH:24][CH:23]=1)[C:4]([N:6]([CH:18]1[CH2:20][CH2:19]1)[CH2:7][C:8]1[C:17]2[C:12](=CC=CC=2)[N:11]=[CH:10][CH:9]=1)=[O:5].O.ON1C2C=C[CH:50]=[CH:51][C:46]=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:64](N(CC)CC)C.CC[O:73][C:74](C)=[O:75]>C(Cl)(Cl)Cl>[CH:18]1([N:6]([CH2:7][C:8]2[CH:17]=[CH:12][N:11]=[CH:10][CH:9]=2)[C:4](=[O:5])[CH:3]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH2:30][O:31][C:32]3[C:37]([Cl:38])=[CH:36][C:35]([CH3:39])=[CH:34][C:33]=3[Cl:40])=[CH:26][CH:27]=2)[CH2:2][NH:1][C:74](=[O:73])[O:75][C:51]([CH3:50])([CH3:46])[CH3:64])[CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 15981190HCID 15981190, compound

Product 1

HCID 86635948tert-Butyl (3-[cyclopropyl(pyridin-4-ylmethyl)amino]-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

3-[tert-Butoxycarbonyl)amino]-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}propanoic acid from Example 9, Step 3 (1 eq.) was combined with 1-hydroxybenzotriazole hydrate (1.5 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide HCl salt (1.5 eq.) in chloroform (0.08 M). To this yellow solution was then added Amine 46 (4 eq.) and triethylamine (1.5 eq.). The resulting brown solution was stirred at RT for 48 h. The reaction solution was diluted with EtOAc and washed with H2O. The aqueous washes were back extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 2:3 (v/v) Hex:EtOAc→EtOAc) afforded the title compound.

Workup

  1. washwashed with H2O
  2. extractionThe aqueous washes were back extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customPurification of the crude product
  8. customthus obtained by way of flash chromatography (SiO2, 2:3 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-7c722dc570d44a3da6cd9bbe03e0152c
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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