Potassium Carbonate → HCID 86707899, compound

HRID 877736Notes

Reaction equation

HRID 877736 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:22][C@@H:14]4[CH2:15][N:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:17][C@@H:13]4[C@H:12]3[CH3:23])=[C:8]([C:24]([NH2:26])=[O:25])[CH:7]=[N:6][N:5]2[CH:27]=1.[C:28](=[O:31])([O-])[O-].[K+].[K+].C[N:35](C)[CH2:36][CH2:37][NH2:38].[O:40]1[CH2:45][CH2:44]OCC1>[Cu]I>[C:45]([N:35]1[CH2:36][CH2:37][N:38]([C:2]2[CH:3]=[C:4]3[C:9]([NH:10][C@@H:11]4[CH2:22][C@@H:14]5[CH2:15][N:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:17][C@@H:13]5[C@H:12]4[CH3:23])=[C:8]([C:24]([NH2:26])=[O:25])[CH:7]=[N:6][N:5]3[CH:27]=2)[C:28]1=[O:31])(=[O:40])[CH3:44]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 66053N,N-DimethylethylenediamineHCID 68291410HCID 68291410, compound

Product 1

HCID 86707899HCID 86707899, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-4-((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 3 of Example 59 (12 mg, 0.026 mmol), 1-acetyllmidazolidin-2-one (6.7 mg, 0.053 mmol), copper(I) iodide (1 mg, 5 mmol), potassium carbonate (7 mg, 0.053 mmol) and N,N-dimethylethane-1,2-diamine (1 μL, 10 mmol) in dioxane (0.8 mL) was sealed under nitrogen in a vial and heated to 100° C. for 3 h. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 0-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (3.3 mg, 25% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.01 (d, J=1.5 Hz, 1H), 4.13-3.98 (m, 1H), 3.97-3.73 (m, 4H), 3.27-3.13 (m, 3H), 3.08 (dd, J=9.7, 3.2 Hz, 1H), 2.95 (s, 3H), 2.82-2.76 (m, 1H), 2.62-2.54 (m, 1H), 2.45 (s, 3H), 2.36-2.26 (m, 1H), 1.63 (td, J=9.7, 6.9 Hz, 1H), 1.41-1.26 (m, 1H), 1.09 (d, J=6.4 Hz, 3H); MS (ES+) m/z: 504.1 (M+H); LC retention time: 1.570 min (analytical HPLC Method M).

Workup

  1. customwas sealed under nitrogen in a vial and
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-075f25a7a8864d578d2767941e67f4b4
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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