Diisopropylethylamine → HCID 131736768, compound

HRID 1485904Notes

Reaction equation

HRID 1485904 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.FC(F)(F)C(O)=O.[F:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[C:58]=1[NH:64][C:65]([C@@H:67]1[CH2:76][C:75]2[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=2)[CH2:69][NH:68]1)=[O:66]>CN(C=O)C.CCOC(C)=O>[F:56][C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[C:58]=1[NH:64][C:65]([C@@H:67]1[CH2:76][C:75]2[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=2)[CH2:69][N:68]1[C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])=[O:66]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90039950HCID 90039950, compound

Product 1

HCID 131736768HCID 131736768, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (60 mg, 277 μmol, Eq: 1.2) and DIEA (120 μL, 693 μmol, Eq: 3) in DMF (1 mL) was added HATU (105 mg, 277 μmol, Eq: 1.2) and the resulting solution stirred at RT for 15 min. (S)—N-(2,6-Difluorophenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide trifluoroacetate (93 mg, 231 μmol, Eq: 1.00) in DMF (1 mL) was then added and stirring was continued at rt. After 1 h, the reaction mixture was diluted with EtOAc and washed with 0.1 M NaOH, 0.1 M HCl, and brine. The organic layer was concentrated in vacuo and the residue azeotroped with n-heptanes to give tert-butyl (S)-1-((S)-3-(2,6-difluorophenylcarbamoyl)-3,4-dihydro isoquinolin-2 (1H)-yl)-3-methyl-1-oxobutan-2-ylcarbamate as a white solid which was used without purification (130 mg), m/z=488 (M+H).

Workup

  1. additionwas then added
  2. customwas continued at rt
  3. washwashed with 0.1 M NaOH, 0.1 M HCl, and brine
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue azeotroped with n-heptanes

Sources & evidence

ORD record
ord-e3d0bfaf15884d5c8843b1ba53fb8f73
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

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