Diisopropylethylamine → HCID 86698425, compound

HRID 527555Notes

Reaction equation

HRID 527555 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C:9]1([C:13]([OH:15])=O)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:49][C:50]1([CH3:67])[C:54]2[C:55]([O:59][C:60]3[N:65]=[CH:64][C:63]([NH2:66])=[CH:62][CH:61]=3)=[CH:56][CH:57]=[CH:58][C:53]=2[O:52][CH2:51]1>CN(C=O)C>[CH3:49][C:50]1([CH3:67])[C:54]2[C:55]([O:59][C:60]3[N:65]=[CH:64][C:63]([NH:66][C:13]([C:9]4([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:10][CH2:11][CH2:12]4)=[O:15])=[CH:62][CH:61]=3)=[CH:56][CH:57]=[CH:58][C:53]=2[O:52][CH2:51]1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 1512646Cyclobutanecarboxylic acid, 1-(((1,1-dimethylethoxy)carbonyl)amino)-3×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 67958060HCID 67958060, compound

Product 1

HCID 86698425HCID 86698425, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclobutanecarboxylic acid (Intermediate 68, 20.16 mg) in dry N,Ndimethylformamide (3 ml), DIPEA (20.44 μl, 0.117 mmol) and then HATU (35.6 mg, 0.094 mmol) were added and the reaction mixture was stirred for 15 minutes at room temperature under argon. Then 6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinamine Intermediate 59, 20 mg) was added and the reaction mixture was stirred at 60° C. under argon during 12 hours. The reaction mixture was cooled down and a prestirred (15 min) solution of HATU (1 equiv), 1-({[(1,1-dimethylethyl)oxy]carbonyl}amino)cyclobutanecarboxylic acid (1 equiv) and DIPEA (1 equiv) in 1 mL of dry DMF was added. The reaction mixture was heated under argon an additional 12 hours at 60° C. The reaction mixture was evaporated. The residue obtained was purified on silica gel (Companion instrument) with cyclohexane/ethylacetate as eluents from 100/0 to 70/30. This afforded the title compound (14 mg)

Workup

  1. stirringthe reaction mixture was stirred at 60° C. under argon during 12 hours
  2. temperatureThe reaction mixture was cooled down
  3. additionwas added
  4. temperatureThe reaction mixture was heated under argon an additional 12 hours at 60° C
  5. customThe reaction mixture was evaporated
  6. customThe residue obtained
  7. customwas purified on silica gel (Companion instrument) with cyclohexane/ethylacetate as eluents from 100/0 to 70/30

Sources & evidence

ORD record
ord-75e1551452e649018e5b16f1c8d8eb5e
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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