Dimethylformamide → HCID 67966832, compound

HRID 1505442Notes

Reaction equation

HRID 1505442 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].CN(C)C=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:42]12([C:48]3[C:49]([O:53][C:54]4[N:59]=[CH:58][C:57]([NH2:60])=[CH:56][CH:55]=4)=[CH:50][CH:51]=[CH:52][C:47]=3[O:46][CH2:45]1)[CH2:44][CH2:43]2>>[C:42]12([C:48]3[C:49]([O:53][C:54]4[N:59]=[CH:58][C:57]([NH:60][C:10]([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH3:14])=[O:12])=[CH:56][CH:55]=4)=[CH:50][CH:51]=[CH:52][C:47]=3[O:46][CH2:45]1)[CH2:44][CH2:43]2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 672354596-(Spiro[1-benzofuran-3,1'-cyclopropan]-4-yloxy)-3-pyridinamine2×

Product 1

HCID 67966832HCID 67966832, compoundYield 89.5%

Procedure

To a solution of (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (94 mg, 0.462 mmol) in dry N,N-Dimethylformamide (2 mL) DIPEA (0.115 mL, 0.661 mmol) and then TBTU (159 mg, 0.496 mmol) were added and the reaction mixture was stirred for 15 minutes at room temperature. 6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinamine (Reference Intermediate 216, 84 mg) was added and the reaction mixture was stirred for 6 hours at the same temperature. The reaction was quenched with brine (2 ml), diluted with water (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was washed with ice cold brine (2×5 ml), dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluents affording the title compound as a colourless oil (130 mg).

Workup

  1. stirringthe reaction mixture was stirred for 6 hours at the same temperature
  2. customThe reaction was quenched with brine (2 ml)
  3. additiondiluted with water (5 ml)
  4. extractionextracted with ethyl acetate (2×10 ml)
  5. washThe organic layer was washed with ice cold brine (2×5 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 7:3 as eluents

Sources & evidence

ORD record
ord-a36df87903664decabac65ebe82680ac
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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