Triethylamine → HCID 66746395, compound

HRID 1467175Notes

Reaction equation

HRID 1467175 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[Cl-].[NH3+:45][C:46]([CH3:65])([CH3:64])[CH2:47][O:48][C:49]1[CH:58]=[CH:57][CH:56]=[C:55]2[C:50]=1[C:51]([NH3+:63])=[C:52]([C:60]([OH:62])=[O:61])[C:53]([CH3:59])=[N:54]2.[Cl-]>CN(C=O)C>[NH2:63][C:51]1[C:50]2[C:55](=[CH:56][CH:57]=[CH:58][C:49]=2[O:48][CH2:47][C:46]([NH:45][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])([CH3:65])[CH3:64])[N:54]=[C:53]([CH3:59])[C:52]=1[C:60]([OH:62])=[O:61]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 6376026-((tert-Butoxycarbonyl)amino)hexanoic acidHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 178432179HCID 178432179, compound

Product 1

HCID 66746395HCID 66746395, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 6-(tert-butoxycarbonylamino)hexanoic acid (0.21 g, 0.90 mmol) in dry DMF (10 mL) was treated with triethylamine (0.46 g, 4.51 mmol, 0.63 mL) and N,N,N′,N′-tetramethyl-O-(N-succinimidyl)uronium tetrafluoroborate (TSTU) (0.30 g, 0.99 mmol) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred at room temperature over 3 h and then a solution of 5-(2-ammonio-2-methylpropoxy)-3-carboxy-2-methylquinolin-4-aminium chloride (Example 152b) (0.33 g, 0.90 mmol) and triethylamine (0.46 g, 4.51 mmol, 0.63 mL) in dry DMF was added dropwise at room temperature. The obtained mixture was stirred at room temperature over 3 days and the solvent was evaporated. The residue was dissolved in a mixture of MeOH and H2O (50 mL, 1:1) and the product was isolated by preparative HPLC (RPC18, H2O→CH3CN gradient). The appropriate fractions were collected and evaporated under reduced pressure. The residue was dried in a dessicator over phosphorus pentoxide to give 0.21 g (45%) of 4-amino-5-(2-(6-(tert-butoxycarbonylamino)hexanamido)-2-methylpropoxy)-2-methylquinoline-3-carboxylic acid as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.95-12.65 (m, 1H), 12.45-11.95 (m, 1H), 9.05-8.60 (m, 1H), 7.84 (s, 1H), 7.67 (t, J=8.0 Hz, 1H), 7.29 (d, J=8.2 Hz, 1H), 7.02 (d, J=8.1 Hz, 1H), 6.71 (t, J=5.6 Hz, 1H), 4.36 (s, 2H), 2.78 (s, 3H), 2.70 (q, J=6.4 Hz, 2H), 2.05 (t, J=7.3 Hz, 2H), 1.45-1.34 (m, 2H), 1.36 (s, 3H), 1.34 (s, 3H), 1.30-1.19 (m, 2H), 1.14-1.03 (m, 2H). MS 503 (MH+).

Workup

  1. stirringThe obtained mixture was stirred at room temperature over 3 days
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in a mixture of MeOH and H2O (50 mL, 1:1)
  4. customthe product was isolated by preparative HPLC (RPC18, H2O→CH3CN gradient)
  5. customThe appropriate fractions were collected
  6. customevaporated under reduced pressure
  7. dry with materialThe residue was dried in a dessicator over phosphorus pentoxide

Sources & evidence

ORD record
ord-df6450bb799449fca3f01db47bfaa772
Source dataset
uspto-grants-2015_04
Patent number
US09000054B2

Reaction notes

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