Diisopropylethylamine → benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate

HRID 709373Notes

Reaction equation

HRID 709373 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[C:18](=[O:19])[N:17]2[C@H:20]([C:24](O)=[O:25])[CH2:21][CH2:22][CH2:23][N:16]2[C:15](=[O:27])[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:53][CH2:54][C:55]([C:57]1[CH:62]=[CH:61][C:60]([Br:63])=[CH:59][CH:58]=1)=[O:56].CCN(C(C)C)C(C)C>[Cl-].[Na+].O.O.CN(C=O)C>[Br:63][C:60]1[CH:61]=[CH:62][C:57]([C:55](=[O:56])[CH2:54][NH:53][C:24]([C@H:20]2[N:17]3[C:18](=[O:19])[C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:13][CH2:14][C:15](=[O:27])[N:16]3[CH2:23][CH2:22][CH2:21]2)=[O:25])=[CH:58][CH:59]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18396550(1S,9S)-9-(benzyloxycarbonylamino)-6,10-dioxo octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid

Product 1

HCID 131733894benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamateYield 78.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In a 50 ml, round-bottomed flask, (1S,9S)-9-(benzyloxycarbonylamino)-6,10-dioxo octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (1 g, 2.66 mmol) was combined with DMF (15 ml) to give a colorless solution. HATU (1.01 g, 2.66 mmol) was added and stirred at room temperature for 10 min. 2-Amino-1-(4-bromophenyl)ethanone HCl (666 mg, 2.66 mmol, Eq: 1.00) and DIPEA (1.03 g, 1.4 ml, 7.99 mmol) were added and stirred at room temperature overnight. The reaction mixture was diluted with brine and H2O and extracted with EtOAc (2×60 ml). The organic layers were combined, washed with brine (2×20 mL), H2O (2×50 mL), dried with MgSO4 and concentrated in vacuo. The crude product was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 6%, 8% MeOH/CH2Cl2) to afford benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate as a light yellow solid (1.2 g, 78.8%). ESI-LRMS m/e calcd for C26H27BrN4O6 [M+] 571. found 572 [M+H+].

Workup

  1. customto give a colorless solution
  2. stirringstirred at room temperature overnight
  3. extractionextracted with EtOAc (2×60 ml)
  4. washwashed with brine (2×20 mL), H2O (2×50 mL)
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 6%, 8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e220c39edd1f42ca9a0e100380fdfa14
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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