Diisopropylethylamine → HCID 178467766, compound

HRID 2202279Notes

Reaction equation

HRID 2202279 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:26]([O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[C@H:35]([C:39]([NH:41][C:42]1[CH:47]=[C:46]([F:48])[C:45]([C:49]([CH3:55])([CH3:54])[CH2:50][O:51][CH2:52][CH3:53])=[C:44]([F:56])[CH:43]=1)=[O:40])[NH:34][CH2:33][CH2:32]2)[CH3:27].[C:57]([O:61][C:62](=[O:71])[CH2:63][C@@H:64]1[CH2:67][C@H:66]([C:68](O)=[O:69])[CH2:65]1)([CH3:60])([CH3:59])[CH3:58].CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:26]([O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[C@H:35]([C:39](=[O:40])[NH:41][C:42]1[CH:47]=[C:46]([F:48])[C:45]([C:49]([CH3:54])([CH3:55])[CH2:50][O:51][CH2:52][CH3:53])=[C:44]([F:56])[CH:43]=1)[N:34]([C:68]([C@@H:66]1[CH2:65][C@H:64]([CH2:63][C:62]([O:61][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:71])[CH2:67]1)=[O:69])[CH2:33][CH2:32]2)[CH3:27]

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 118622710(R)-6-ethoxy-N-(4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochlorideHCID 178451083HCID 178451083, compound

Product 1

HCID 178467766HCID 178467766, compoundYield 97.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (90 mg, 0.24 mmol) was added to a solution of (R)-6-ethoxy-N-(4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamide hydrochloride (101 mg, 0.22 mmol), cis-3-(2-(tert-butoxy)-2-oxoethyl)cyclobutanecarboxylic acid (50.8 mg, 0.24 mmol) and DIEA (0.085 mL, 0.47 mmol) in DMF (2 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; 3→50% ethyl acetate/hexane) to give tert-butyl 2-(cis-3-((R)-6-ethoxy-1-((4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluorophenyl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)cyclobutyl)acetate (135 mg, 0.215 mmol, quant.).

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; 3→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-743209d95deb4b9b9e178c66fb643661
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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