Trifluoroacetic acid → 4-[9-(Benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoic acid

HRID 2230455Notes

Reaction equation

HRID 2230455 reaction equation
[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:35]=[O:36])[CH2:26][CH2:27][C:28]([O:30]C(C)(C)C)=[O:29])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:37])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]([NH:9][CH:10]1[C:16](=[O:17])[N:15]2[CH:18]([C:22]([NH:24][CH:25]([CH:35]=[O:36])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:23])[CH2:19][CH2:20][CH2:21][N:14]2[C:13](=[O:37])[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 54215480t-Butyl 4-[9-(benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino-[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoate

Product 1

HCID 543661774-[9-(Benzoylamino)-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxamido]-5-oxopentanoic acidYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of t-butyl ester 234e (179 mg, 0.35 mmol) in dry CH2Cl2 (3 ml) was cooled to 0° C. and treated with trifluoroacetic acid (2 ml). The resultng solution was stirred at 0° C. for 30 min and then at room temperature for 2 h. The solution was concentrated, the residue taken up in dry CH2Cl2 (5 ml) and the mixture again concentrated. This process was repeated once again with more CH2Cl2 (5 ml). The residue obtained was crystallized in diethyl ether. The precipitate was collected and purified on silica gel column (5% methanol in CH2Cl2) which afforded compound 235e as a white solid (111 mg, 70%): mp 142° C. (dec); [α]D20 −85.5 (c 0.062, MeOH); IR (KBr) 3409, 3075, 2952, 1651, 1541, 1424, 1280, 1198, 1136, 717; 1H NMR (D6-DMSO) δ9.40 (1H, s), 8.62 (2H, m), 7.96-7.38 (5H, m), 5.19-5.02 (1H, m), 4.98-4.79 (1H, m), 4.48-4.19 (1H, m), 3.51-3.11 (2H, m), 3.04-2.90 (2H, m), 2.38-1.46 (10H, m).

Workup

  1. waitat room temperature for 2 h
  2. concentrationThe solution was concentrated
  3. concentrationthe mixture again concentrated
  4. customThe residue obtained
  5. customwas crystallized in diethyl ether
  6. customThe precipitate was collected
  7. custompurified on silica gel column (5% methanol in CH2Cl2) which

Sources & evidence

ORD record
ord-def3bf2e199949dbb7c9c33d4271c610
Source dataset
uspto-grants-2002_07
Patent number
US06423840B1

Reaction notes

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