Dimethylformamide → tert-butyl N-[(1R)-1-[[6-[(2,2-dimethyl-3H-benzofuran-4-yl)oxy]-3-pyridyl]carbamoyl]propyl]carbamate

HRID 527665Notes

Reaction equation

HRID 527665 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].CCN([CH:21]([CH3:23])[CH3:22])C(C)C.CN(C(ON1N=[N:39][C:34]2[CH:35]=[CH:36][CH:37]=[N:38][C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC1(C)[C:53]2[C:54]([O:58]C3N=CC(N)=CC=3)=[CH:55][CH:56]=[CH:57][C:52]=2[O:51]C1.[CH3:67]N(C=O)C>>[CH3:67][C:21]1([CH3:22])[CH2:23][C:53]2[C:54]([O:58][C:37]3[N:38]=[CH:33][C:34]([NH:39][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:35][CH:36]=3)=[CH:55][CH:56]=[CH:57][C:52]=2[O:51]1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2755936(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679580606-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinamine2×

Product 1

HCID 86698460tert-butyl N-[(1R)-1-[[6-[(2,2-dimethyl-3H-benzofuran-4-yl)oxy]-3-pyridyl]carbamoyl]propyl]carbamate

Procedure

To a solution of (2R)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)butanoic acid (17.84 mg, 0.088 mmol) in dry N,Ndimethylformamide (DMF) (1 mL), DIPEA (25.6 μl, 0.146 mmol) and then HATU (37.8 mg, 0.099 mmol) were added and the reaction mixture was stirred for 15 minutes at room temperature under argon. Then 6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinamine (Intermediate 207, 15 mg, 0.059 mmol) was added and the reaction mixture was left overnight under stirring at 35° C. under argon. The reaction mixture was evaporated. Brine (4 ml) was added and it was extracted 3 times with ethyl acetate (3×5 ml). Combined organic layers were dried over Na2SO4, filtered and evaporated and the residue was purified by flash chromatography (Companion system, 12 g silica cartridge) with cyclohexane/ethyl acetate as eluents from 100:0 to 70:30 affording the title compound (18 mg).

Workup

  1. waitthe reaction mixture was left overnight
  2. stirringunder stirring at 35° C. under argon
  3. customThe reaction mixture was evaporated
  4. additionBrine (4 ml) was added
  5. extractionit was extracted 3 times with ethyl acetate (3×5 ml)
  6. dry with materialCombined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customthe residue was purified by flash chromatography (Companion system, 12 g silica cartridge) with cyclohexane/ethyl acetate as eluents from 100:0 to 70:30 affording the title compound (18 mg)

Sources & evidence

ORD record
ord-b5ecf48ba2a44ea7a87eb71bb29a1b8c
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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