Diisopropylethylamine → HCID 178487217, compound

HRID 2202218Notes

Reaction equation

HRID 2202218 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][CH3:51])=[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:61]1([C:68](O)=[O:69])[CH2:64][C@@H:63]([C:65]([OH:67])=[O:66])[CH2:62]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][CH3:51])=[CH:47][CH:48]=3)[CH2:43][CH2:42][N:41]2[C:68]([C@@H:61]2[CH2:64][C@H:63]([C:65]([OH:67])=[O:66])[CH2:62]2)=[O:69])=[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 131735726(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamideHCID 178525793HCID 178525793, compound

Product 1

HCID 178487217HCID 178487217, compoundYield 32.1%

Reagents, catalysts & solvents 3

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

Procedure

HATU (82 mg, 0.22 mmol) was added to a solution of (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxamide (70 mg, 0.18 mmol), DIEA (0.061 mL, 0.36 mmol) and cis-cyclobutane-1,3-dicarboxylic acid (78 mg, 0.54 mmol) in DMF (2.0 mL) at room temperature, and the mixture was stirred overnight at room temperature. 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 (29.7 mg, 0.057 mmol, 32.1%) 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-d48d0e7116fe476eae460566e784dcf3
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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