Diisopropylethylamine → HCID 178487214, compound

HRID 2202309Notes

Reaction equation

HRID 2202309 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:27]=[C:28]([NH:36][C:37]([C@H:39]2[C:48]3[C:43](=[CH:44][C:45]([O:49][CH3:50])=[CH:46][CH:47]=3)[CH2:42][CH2:41][NH:40]2)=[O:38])[CH:29]=[CH:30][C:31]=1[Si:32]([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.[C:60]([O:64][C:65](=[O:74])[CH2:66][C@H:67]1[CH2:70][C@H:69]([C:71](O)=[O:72])[CH2:68]1)([CH3:63])([CH3:62])[CH3:61]>CN(C=O)C.O>[F:25][C:26]1[CH:27]=[C:28]([NH:36][C:37]([C@H:39]2[C:48]3[C:43](=[CH:44][C:45]([O:49][CH3:50])=[CH:46][CH:47]=3)[CH2:42][CH2:41][N:40]2[C:71]([C@H:69]2[CH2:68][C@H:67]([CH2:66][C:65]([O:64][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:74])[CH2:70]2)=[O:72])=[O:38])[CH:29]=[CH:30][C:31]=1[Si:32]([CH3:33])([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131735755(R)-N-(3-fluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamideHCID 178451084HCID 178451084, compound

Product 1

HCID 178487214HCID 178487214, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (86 mg, 0.23 mmol) was added to a solution of (R)—N-(3-fluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide (70 mg, 0.19 mmol), DIEA (0.064 mL, 0.38 mmol) and trans-3-(2-(tert-butoxy)-2-oxoethyl)cyclobutanecarboxylic acid (42.3 mg, 0.20 mmol) in DMF (2.0 mL) at room temperature, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 20→50% ethyl acetate/hexane) to give tert-butyl 2-(trans-3-((R)-1-((3-fluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate (92.3 mg, 0.162 mmol, 86%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 20→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a2c685727bf34b7e9ea0919241f1bffc
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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