Diisopropylethylamine → HCID 178465951, compound

HRID 2202250Notes

Reaction equation

HRID 2202250 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:37][C:38]([C@H:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH2:51][CH3:52])=[CH:47][CH:48]=3)[CH2:43][CH2:42][NH:41]2)=[O:39])[CH:29]=[C:30]([F:36])[C:31]=1[Si:32]([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.[C@H:62]1([C:69](O)=[O:70])[CH2:65][C@@H:64]([C:66]([OH:68])=[O:67])[CH2:63]1>CN(C=O)C.O.C(#N)C.O>[F:25][C:26]1[CH:27]=[C:28]([NH:37][C:38]([C@H:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH2:51][CH3:52])=[CH:47][CH:48]=3)[CH2:43][CH2:42][N:41]2[C:69]([C@@H:62]2[CH2:65][C@H:64]([C:66]([OH:68])=[O:67])[CH2:63]2)=[O:70])=[O:39])[CH:29]=[C:30]([F:36])[C:31]=1[Si:32]([CH3:33])([CH3:35])[CH3:34]

Participants

8

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 131735735(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-ethoxy-1,2, 3,4-tetrahydroisoquinoline-1-carboxamideHCID 178525793HCID 178525793, compound

Product 1

HCID 178465951HCID 178465951, compoundYield 28.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

HATU (226 mg, 0.59 mmol) was added to a solution of (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide (200 mg, 0.49 mmol), DIEA (0.169 mL, 0.99 mmol) and cis-cyclobutane-1,3-dicarboxylic acid (214 mg, 1.48 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→90% ethyl acetate/hexane), and then preparative HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)) to give the title compound (74.8 mg, 0.141 mmol, 28.5%) 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→90% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f6cc1e1d8bb847bab9bb5ab07edf0fd4
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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