Diisopropylethylamine → HCID 67966958, compound

HRID 527560Notes

Reaction equation

HRID 527560 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][C:51]1([CH3:68])[C:55]2[C:56]([O:60][C:61]3[N:66]=[CH:65][C:64]([NH2:67])=[CH:63][N:62]=3)=[CH:57][CH:58]=[CH:59][C:54]=2[O:53][CH2:52]1>>[CH3:50][C:51]1([CH3:68])[C:55]2[C:56]([O:60][C:61]3[N:62]=[CH:63][C:64]([NH:67][C:14]([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[C:10]([CH3:11])([CH3:12])[CH3:13])=[O:16])=[CH:65][N:66]=3)=[CH:57][CH:58]=[CH:59][C:54]=2[O:53][CH2:52]1

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acid2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679585232-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinamine2×

Product 1

HCID 67966958HCID 67966958, compoundYield 31%

Procedure

To a solution of N-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-D-valine (Intermediate 76, 53.9 mg) in dry N,Ndimethylformamide (1 ml), DIPEA (50.9 μl, 0.292 mmol) and then HATU (102 mg, 0.268 mmol) were added and the reaction mixture was stirred for 15 minutes at room temperature under argon. Then 2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinamine (Intermediate 65, 30 mg) was added and the reaction mixture was stirred at 60° C. under argon during 12 hours. The reaction was quenched with brine (1 ml), diluted with water (2 ml) and extracted with ethyl acetate (2×5 ml). The organic layer was dried over sodium sulphate and evaporated. The residue obtained was purified on silica gel (Companion instrument) with a gradient cyclohexane/ethylacetate 100/0 to 70/30. This afforded the title compound (17 mg).

Workup

  1. stirringthe reaction mixture was stirred at 60° C. under argon during 12 hours
  2. customThe reaction was quenched with brine (1 ml)
  3. additiondiluted with water (2 ml)
  4. extractionextracted with ethyl acetate (2×5 ml)
  5. dry with materialThe organic layer was dried over sodium sulphate
  6. customevaporated
  7. customThe residue obtained
  8. customwas purified on silica gel (Companion instrument) with a gradient cyclohexane/ethylacetate 100/0 to 70/30

Sources & evidence

ORD record
ord-8ed842a466c5442a9f955d28ba2f0341
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

Loading…