N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanine → 1,1-Dimethylethyl (1,1-dimethyl-2-oxo-2-{[6-(spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)-3-pyridinyl]amino}ethyl)carbamate

HRID 1023635Notes

Reaction equation

HRID 1023635 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C:9]([CH3:14])([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:39]12([C:45]3[C:46]([O:50][C:51]4[N:56]=[CH:55][C:54]([NH2:57])=[CH:53][CH:52]=4)=[CH:47][CH:48]=[CH:49][C:44]=3[O:43][CH2:42]1)[CH2:41][CH2:40]2>CN(C)C=O>[CH3:14][C:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:10])[C:11](=[O:13])[NH:57][C:54]1[CH:55]=[N:56][C:51]([O:50][C:46]2[C:45]3[C:39]4([CH2:42][O:43][C:44]=3[CH:49]=[CH:48][CH:47]=2)[CH2:41][CH2:40]4)=[CH:52][CH:53]=1

Participants

5

Reactant 3

HCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672354596-(Spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)-3-pyridinamine2×

Product 1

HCID 683224941,1-Dimethylethyl (1,1-dimethyl-2-oxo-2-{[6-(spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)-3-pyridinyl]amino}ethyl)carbamateYield 75.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-methylalanine (80 mg, 0.393 mmol) in dry N,N-dimethylformamide (1.5 mL) DIPEA (0.096 mL, 0.551 mmol) and then HATU (150 mg, 0.393 mmol) were added and the reaction mixture was stirred for 15 minutes at room temperature. This solution was added to a solution of 6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinamine (Reference Intermediate 218, 40 mg) in dry N,N-dimethylformamide (0.5 ml) and the reaction mixture was stirred overnight at room temperature. The reaction was quenched with water (2 ml), diluted with brine (10 ml) and extracted with ethyl acetate (2×20 ml). The organic layer was dried over sium sulphqte, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents affording the title compound as a white solid (52 mg).

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. customThe reaction was quenched with water (2 ml)
  3. additiondiluted with brine (10 ml)
  4. extractionextracted with ethyl acetate (2×20 ml)
  5. customThe organic layer was dried over sium sulphqte
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents

Sources & evidence

ORD record
ord-a65676f2808842ad9b65d43fb1e177d3
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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