Water → HCID 46847343, compound

HRID 1907340Notes

Reaction equation

HRID 1907340 reaction equation
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Cl[C:37]1[CH:38]=[CH:39][C:40]2[N:41]([CH:43]=[CH:44][N:45]=2)[N:42]=1.C([O-])(O)=O.[Na+].O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[CH:38]=[CH:39][C:40]4[N:41]([CH:43]=[CH:44][N:45]=4)[N:42]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

7

Reactant 4

HCID 962WaterHCID 138828Imidazo(1,2-b)pyridazine, 6-chloro-HCID 516892Sodium BicarbonateHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 46847343HCID 46847343, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A microwave vial equipped with a flea stir bar was charged with (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborol-an-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (20 mg, 0.042 mmol), 6-chloroimidazo[1,2-b]pyridazine (13 mg, 0.083 mmol), NaHCO3 (7 mg, 0.083 mmol), PdCl2(dppf) (3 mg, 0.004 mmol), H2O (0.1 mL) and dry dioxane (1.0 mL). The mixture was sparged with nitrogen for 10 min and heated at 110° C. for 30 min in the microwave. The mixture was diluted with glacial HOAc (0.1 mL) and methanol (0.6 mL), and filtered. The filtrate was purified directly by prep HPLC to afford the title compound (12.8 mg, 65%) as an oil. LC-MS Method 1 tR=1.28 min, m/z=471; 1H NMR (CD3OD) 0.97 (s, 3H), 1.26 (s, 3H), 1.59 (d, 3H), 2.17 (s, 2H), 2.29 (m, 1H), 2.50 (2H), 3.11 (m, 1H), 5.61 (q, 1H), 7.19 (d, 2H), 7.25-7.40 (5H), 7.93 (d, 2H), 8.19 (s, 1H), 8.27 (d, 1H), 8.42 (d, 1H), 8.54 (s, 1H).

Workup

  1. customA microwave vial equipped with a flea
  2. customThe mixture was sparged with nitrogen for 10 min
  3. additionThe mixture was diluted with glacial HOAc (0.1 mL) and methanol (0.6 mL)
  4. filtrationfiltered
  5. customThe filtrate was purified directly by prep HPLC

Sources & evidence

ORD record
ord-a6e11299cde44ab593f4654cc625e062
Source dataset
uspto-grants-2013_12
Patent number
US08598163B2

Reaction notes

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