Diisopropylethylamine → HCID 178487613, compound

HRID 2202303Notes

Reaction equation

HRID 2202303 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[NH:49][CH2:48][CH2:47][C:46]3[N:45]=[C:44]([O:50][CH3:51])[CH:43]=[CH:42][C:41]2=3)=[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.C(=O)([O-])O.[Na+]>CN(C=O)C.O.C(#N)C>[F:36][C:30]1[CH:29]=[C:28]([NH:37][C:38]([C@@H:40]2[N:49]([C:68]([C@@H:61]3[CH2:64][C@H:63]([C:65]([OH:67])=[O:66])[CH2:62]3)=[O:69])[CH2:48][CH2:47][C:46]3[N:45]=[C:44]([O:50][CH3:51])[CH:43]=[CH:42][C:41]2=3)=[O:39])[CH:27]=[C:26]([F:25])[C:31]=1[Si:32]([CH3:35])([CH3:34])[CH3:33]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131735740(R)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamideHCID 178525793HCID 178525793, compound

Product 1

HCID 178487613HCID 178487613, compoundYield 38.5%

Reagents, catalysts & solvents 2

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

Procedure

HATU (82 mg, 0.21 mmol) was added to a solution of (R)—N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamide (70 mg, 0.18 mmol), DIEA (0.061 mL, 0.36 mmol) and cis-cyclobutane-1,3-dicarboxylic acid (38.7 mg, 0.27 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 aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, 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→490% ethyl acetate/hexane), and then preparative HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)) to give the title compound (35.6 mg, 0.069 mmol, 38.5%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water
  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→490% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-db4b561f4ed64eb1a2e1840b79d7b887
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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