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 527571Notes

Reaction equation

HRID 527571 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 (Intermediate 89, 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 sodium sulphate, 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. dry with materialThe organic layer was dried over sodium sulphate
  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-ffebece09e82476494236d20f6845022
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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