Triphenylphosphine → HCID 71606413, compound

HRID 2207470Notes

Reaction equation

HRID 2207470 reaction equation
[CH3:1][O:2][C:3]1[C:30]([O:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C:38]2[CH:42]=[C:41]([C:43](=[O:61])[NH:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]4[CH:55]=[C:54]([C:56]([O:58][CH3:59])=[O:57])[N:53]([CH3:60])[CH:52]=4)=[CH:47][CH:46]=3)[N:40]([CH3:62])[CH:39]=2)=[O:36])=[CH:29][C:6]2[N:7](C(OCC=C)=O)[C@@H:8](OC3CCCCO3)[C@@H:9]3[CH2:15][CH2:14][CH2:13][N:10]3[C:11](=[O:12])[C:5]=2[CH:4]=1.N1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]1[C:30]([O:31][CH2:32][CH2:33][CH2:34][C:35]([NH:37][C:38]2[CH:42]=[C:41]([C:43]([NH:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]4[CH:55]=[C:54]([C:56]([O:58][CH3:59])=[O:57])[N:53]([CH3:60])[CH:52]=4)=[CH:47][CH:46]=3)=[O:61])[N:40]([CH3:62])[CH:39]=2)=[O:36])=[CH:29][C:6]2[N:7]=[CH:8][C@@H:9]3[CH2:15][CH2:14][CH2:13][N:10]3[C:11](=[O:12])[C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 31268PyrrolidineHCID 131735922(11S,11aS)-allyl 7-methoxy-8-(4-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-4-oxobutoxy)-5-oxo-11-((tetrahydro-2H-pyran-2-yl)oxy)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate

Product 1

HCID 71606413HCID 71606413, compoundYield 34.3%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

Palladium tetrakis[triphenylphosphine](12.17 mg, 10.5 μM, 0.05 equiv) was added to a solution of Alloc-THP-PBD conjugate 15e (179 mg, 0.21 mmol), pyrrolidine (17.91 mg, 0.25 mmol, 1.2 eq) and triphenylphosphine (13.81 mg, 0.25 equiv) in DCM (5 mL). The reaction mixture was stirred at room temperature for 2 h at which point TLC showed completion of reaction. Excess DCM was removed by rotary evaporation under reduced pressure and the resulting residue dried in vacuo to remove pyrrolidone. The product was purified by high performance liquid chromatography (eluted with acetone:water gradient with 1% TFA) to give the product as a light yellowish solid, 16e (48 mg, 34% after HPLC purification).

Workup

  1. customcompletion of reaction
  2. customExcess DCM was removed by rotary evaporation under reduced pressure
  3. customthe resulting residue dried in vacuo
  4. customto remove pyrrolidone
  5. customThe product was purified by high performance liquid chromatography (eluted with acetone:water gradient with 1% TFA)

Sources & evidence

ORD record
ord-74358d3c79f74639bcd1eb6b246b01d0
Source dataset
uspto-grants-2016_06
Patent number
US09376440B2

Reaction notes

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