Diisopropylethylamine → {(S)-1-[(S)-1-(5-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 1481902Notes

Reaction equation

HRID 1481902 reaction equation
[N:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:7])[C@H:2]([C:4]([OH:6])=O)[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.FC(F)(F)C(O)=O.[NH2:55][C@@H:56]1[C:62](=[O:63])[N:61]([CH2:64][C:65]2[C:74]3[C:69](=[C:70]([Br:75])[CH:71]=[CH:72][CH:73]=3)[CH:68]=[CH:67][C:66]=2[O:76][CH3:77])[C:60]2[CH:78]=[CH:79][CH:80]=[CH:81][C:59]=2[NH:58][CH2:57]1>CN(C=O)C.O>[C:11]([O:10][C:8](=[O:9])[N:1]([C@H:2]([C:4](=[O:6])[NH:55][C@@H:56]1[C:62](=[O:63])[N:61]([CH2:64][C:65]2[C:74]3[C:69](=[C:70]([Br:75])[CH:71]=[CH:72][CH:73]=3)[CH:68]=[CH:67][C:66]=2[O:76][CH3:77])[C:60]2[CH:78]=[CH:79][CH:80]=[CH:81][C:59]=2[NH:58][CH2:57]1)[CH3:3])[CH3:7])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118677404(S)-3-amino-1-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one trifluoroacetate

Product 1

HCID 90220831{(S)-1-[(S)-1-(5-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl esterYield 95.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Boc-N-Me-Ala-OH (107.91 mg, 0.532 mmol), DIPEA (0.251 mL, 1.45 mmol) and HATU (220.37 mg, 0.58 mmol) were added to a solution of (S)-3-amino-1-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one trifluoroacetate (260 mg) in DMF (4 mL) at 0° C. After 3 h the mixture was diluted with water and extracted with ethyl acetate. The extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate solution, dried and concentrated. The residue was purified by silica gel chromatography to afford the title compound (282 mg, 51%) as an off white solid. LC-MS: 613.2 (M+H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extracts were washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate solution
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-56040588c61f4e719e35579a8c51f87a
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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