Triethylamine → HCID 89649155, compound

HRID 1773939Notes

Reaction equation

HRID 1773939 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C([O:40][C:41](=[O:62])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[C:45]([C:51]2[CH:52]=[CH:53][C:54]([F:61])=[C:55]3[C:60]=2[CH2:59][NH:58][CH2:57][CH2:56]3)[CH:44]=1)C.C(N(CC)CC)C>C(Cl)Cl>[F:61][C:54]1[CH:53]=[CH:52][C:51]([C:45]2[CH:44]=[C:43]([CH2:42][C:41]([OH:62])=[O:40])[CH:48]=[CH:47][C:46]=2[O:49][CH3:50])=[C:60]2[C:55]=1[CH2:56][CH2:57][N:58]([C:10](=[O:12])[CH2:9][C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)([CH3:14])[CH3:13])[CH2:59]2

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23293615339-34-4HCID 89648477HCID 89648477, compound

Product 1

HCID 89649155HCID 89649155, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(4-fluoro-phenyl)-3-methyl-butyric acid (20 mg, 0.1 mmol, 1.0 eq.) in DCM (1 mL), 1-hydroxybenzotriazole hydrate (HOBt) (14 mg, 0.1 mmol, 1.0 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol, 1.0 eq.) were added in sequence. The resulting solution was stirred at r.t. for 2 minutes. Then a solution of [3-(5-fluoro-1,2,3,4-tetrahydro-isoquinolin-8-yl)-4-methoxy-phenyl]-acetic acid ethyl ester (34 mg, 0.1 mmol, 1.0 eq.) and triethylamine (42 μL, 0.3 mmol, 3.0 eq.) in DCM (1 mL) was added and the resulting mixture was stirred at r.t. for 18 hours. The mixture was concentrated in vacuo. The residue was dissolved in DMF (0.8 mL). 1M aq. NaOH (1 mL) was added. The mixture was stirred at r.t. for 3 hours. The solution was carefully neutralized with formic acid (0.5 mL), and purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound as a white solid.

Workup

  1. stirringthe resulting mixture was stirred at r.t. for 18 hours
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in DMF (0.8 mL)
  4. addition1M aq. NaOH (1 mL) was added
  5. stirringThe mixture was stirred at r.t. for 3 hours
  6. custompurified by prep
  7. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Sources & evidence

ORD record
ord-da105678e5154341966649d8fd095225
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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