Diisopropylethylamine → N-(3-(2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetamido)propyl)-5-((4S)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

HRID 1525415Notes

Reaction equation

HRID 1525415 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:20])[CH2:7][CH2:8][CH2:9][CH2:10][C@H:11]1[C@@H:18]2[C@@H:14]([NH:15][C:16](=[O:19])[NH:17]2)[CH2:13][S:12]1.FC(F)(F)C(O)=O.NCCCNC(=O)CCCC[C@H]1[C@@H]2[C@@H](NC(N2)=O)CS1.CCN(C(C)C)C(C)C.[Cl:57][C:58]1[C:63]([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)=[N:62][N:61]=[C:60]2[N:70]([CH2:79][C:80](O)=[O:81])[N:71]=[C:72]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[C:59]=12.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[Cl:57][C:58]1[C:63]([C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=2)=[N:62][N:61]=[C:60]2[N:70]([CH2:79][C:80]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:20])[CH2:7][CH2:8][CH2:9][CH2:10][C@H:11]3[CH:18]4[CH:14]([NH:15][C:16](=[O:19])[NH:17]4)[CH2:13][S:12]3)=[O:81])[N:71]=[C:72]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[C:59]=12

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 16218435N-(3-Aminopropyl)biotinamide trifluoroacetateHCID 16218436N-(3-aminopropyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamideHCID 665757822-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid

Product 1

HCID 86697019N-(3-(2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetamido)propyl)-5-((4S)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-aminopropyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide (also known as N-(3-Aminopropyl)biotinamide trifluoroacetate, commercially available from Sigma-Aldrich or J&K Scientific Ltd) (0.22 mmol) in anhydrous DMF (1.1 mL) were sequentially added DIPEA (57 μL, 0.33 mmol), 2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetic acid (80 mg, 0.22 mmol) and 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, commercially available from Sigma-Aldrich or Novabiochem) (125 mg, 0.33 mmol). The reaction mixture was stirred at room temperature for 2 h, then diluted with ethyl acetate and washed with aqueous NaHCO3 and 4% aqueous LiCl. The organic phase was then dried over MgSO4, and evaporated under vacuum. The residue was purified by preparative HPLC yielding Compound 44 as a beige solid (34 mg).

Workup

  1. washwashed with aqueous NaHCO3 and 4% aqueous LiCl
  2. dry with materialThe organic phase was then dried over MgSO4
  3. customevaporated under vacuum
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-f781453c138e442888b1c9bb67ca8055
Source dataset
uspto-grants-2015_07
Patent number
US09079909B2

Reaction notes

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