Acetic Acid → HCID 178502268, compound

HRID 709350Notes

Reaction equation

HRID 709350 reaction equation
COC(N[C@@H]1C(=O)N2[C@H](C(O)=O)CCCN2C(=O)CC1)=O.BrC1C=C(N)C(N)=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:64][O:65][C:66](=[O:92])[NH:67][C@H:68]1[CH2:74][CH2:73][C:72](=[O:75])[N:71]2[CH2:76][CH2:77][CH2:78][C@@H:79]([C:80](=O)[NH:81][C:82]3[CH:87]=[CH:86][C:85]([Br:88])=[CH:84][C:83]=3[NH2:89])[N:70]2[C:69]1=[O:91].C(O)(=O)C>CN(C=O)C.C(OCC)(=O)C>[CH3:64][O:65][C:66](=[O:92])[NH:67][C@H:68]1[CH2:74][CH2:73][C:72](=[O:75])[N:71]2[CH2:76][CH2:77][CH2:78][C@@H:79]([C:80]3[NH:81][C:82]4[CH:87]=[CH:86][C:85]([Br:88])=[CH:84][C:83]=4[N:89]=3)[N:70]2[C:69]1=[O:91]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 3235934-Bromobenzene-1,2-diamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70663807(1S,9S)-9-(methoxycarbonylamino)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acidHCID 89501605[(4S,7S)-4-(2-Amino-4-bromo-phenylcarbamoyl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl]-carbamic acid methyl ester

Product 1

HCID 178502268HCID 178502268, compoundYield 79.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

A solution of (1S,9S)-9-(methoxycarbonylamino)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (184.7 mg, 605 μmol), 4-bromobenzene-1,2-diamine (124 mg, 665 μmol), HATU (230 mg, 605 μmol, Eq: 1.00) in DMF (3 ml) was treated with N,N′-diisopropylethylamine (235 mg, 317 μl, 1.81 mmol, Eq: 3.00). The solution was stirred at 23° C. for 16 h. The reaction mixture was diluted with ethyl acetate, washed with water, brine and dried over MgSO4. The organic layer was concentrated to yield 317.3 mg a 1:1 mixture of [(4S,7S)-4-(2-Amino-4-bromo-phenylcarbamoyl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl]-carbamic acid methyl ester and [(4S,7S)-4-(2-Amino-5-bromo-phenylcarbamoyl)-6,10-dioxo-octahydro-pyridazino[1,2a][1,2]diazepin-7-yl]-carbamic acid methyl ester, as a light brown solid. This mixture was used as such for the next step. A solution of the mixture (317 mg, 508 μmol) in acetic acid (3.12 g, 3 mL, 52.0 mmol) was heated for 1 hr at 90° C. The reaction mixture was cooled to 23° C., and concentrated in vacuo. The residue was dissolved in ethyl acetate (30 mL) washed with sat. NaHCO3, brine and dried (MgSO4). The organic layer was concentrated to yield [(4S,7S)-4-(5-bromo-1H-benzoimidazol-2-yl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl]-carbamic acid methyl ester as light brown powder (191.3 mg, 79.5%). ESI-LRMS m/e calcd for C18H20BrN5O4 [M+] 449. found 450 [M+H1].

Workup

  1. washwashed with water, brine
  2. dry with materialdried over MgSO4
  3. concentrationThe organic layer was concentrated
  4. customto yield
  5. temperatureThe reaction mixture was cooled to 23° C.
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in ethyl acetate (30 mL)
  8. washwashed with sat. NaHCO3, brine
  9. dry with materialdried (MgSO4)
  10. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-fb5b24e642234676ae061060cd5dd49b
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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