Hydrochloric Acid → 6-bromo-4-((3S,4S)-1-(2-cyanoacetyl)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877771Notes

Reaction equation

HRID 877771 reaction equation
I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH3:17])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:18]([NH2:20])=[O:19])[CH:8]=[N:7][N:6]2[CH:21]=1.[C:22]([CH2:24][C:25](O)=[O:26])#[N:23].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH3:17])[CH2:15][N:14]([C:25](=[O:26])[CH2:24][C:22]#[N:23])[CH2:13]3)=[C:9]([C:18]([NH2:20])=[O:19])[CH:8]=[N:7][N:6]2[CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 682912146-bromo-4-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide

Product 1

HCID 682912086-bromo-4-((3S,4S)-1-(2-cyanoacetyl)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To solution of 6-bromo-4-((3S,4S)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydrogen iodide salt prepared as previously described in Step 1 of Example 158 (200 mg, 0.429 mmol), 2-cyanoacetic acid (43.8 mg, 0.515 mmol) and BOP (285 mg, 0.644 mmol) in DMF (2 mL) was added DIPEA (0.225 mL, 1.288 mmol) and the resulting mixture was stirred at rt for 4 h. The reaction mixture was added to water (˜5 volumes) and the pH was adjusted to ˜7 with 1 N HCl and the resulting cloudy mixture was extracted with EtOAc (150 mL×2). The combined organic extracts were washed with water, brine, dried over anhyd. magnesium sulfate, filtered and concentrated to afford the title compound which was used directly in the next transformation. HPLC (method B) retention time=2.55 min. LCMS (m+1)=405.

Workup

  1. extractionthe resulting cloudy mixture was extracted with EtOAc (150 mL×2)
  2. washThe combined organic extracts were washed with water, brine
  3. customdried over anhyd
  4. filtrationmagnesium sulfate, filtered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-68bb7580611b4c6c8a6f07d4d9932dd9
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…