Diisopropylethylamine → HCID 68322478, compound

HRID 1505359Notes

Reaction equation

HRID 1505359 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C:9]([CH3:14])([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])[CH3:3].C(N(C(C)C)C(C)C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH2:46]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[O:54][C:55]1[N:60]=[CH:59][C:58]([NH2:61])=[CH:57][CH:56]=1)[CH3:47]>CN(C)C=O>[CH2:46]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[O:54][C:55]1[N:60]=[CH:59][C:58]([NH:61][C:11](=[O:13])[C:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:10])[CH3:14])=[CH:57][CH:56]=1)[CH3:47]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 28818304HCID 28818304, compound2×

Product 1

HCID 68322478HCID 68322478, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 8 mL vial N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-methylalanine (208 mg, 1.022 mmol) was dissolved in N,N-dimethylformamide (4 mL) to give a colourless solution. N-ethyl-N-(1-methylethyl)-2-propanamine (0.223 mL, 1.277 mmol) and N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylidene]-N-methylmethanaminium tetrafluoroborate (328 mg, 1.022 mmol) were added. The reaction mixture was stirred at room temperature for 15 min. 6-[(2-ethylphenyl)oxy]-3-pyridinamine (Intermediate 46, 228 mg) was added and the reaction mixture was warmed to 60° C. After 24 hours, additional 150 mg of N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylidene]-N-methylmethanaminium tetrafluoroborate were added. After additional 8 hours, the solvent was evaporated under vacuum using the Genevac affording a dark brown oil which was purified by silica gel chromatography (Biotage system, 25 g SNAP column) with as eluent a gradient Cyclohexane/EtOAc from 3:1 to 1:1 in 10 CV, then 1:1 for 5 CV. The collected fractions afforded the title compound as a pale orange solid (88.6 mg).

Workup

  1. customto give a colourless solution
  2. temperaturethe reaction mixture was warmed to 60° C
  3. waitAfter 24 hours
  4. waitAfter additional 8 hours
  5. customthe solvent was evaporated under vacuum
  6. customaffording a dark brown oil which
  7. customwas purified by silica gel chromatography (Biotage system, 25 g SNAP column) with as eluent a gradient Cyclohexane/EtOAc from 3:1 to 1:1 in 10 CV

Sources & evidence

ORD record
ord-083a195381744808a3f1391a4fc9401f
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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