Acetonitrile → HCID 86696491, compound

HRID 870784Notes

Reaction equation

HRID 870784 reaction equation
[NH2:1][C@@H:2]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]3[N:15]([C:17](Br)=[CH:18][N:19]=3)[N:16]=2)[CH2:7][CH2:6]1)=[O:4].[CH3:25][O:26][C:27]1[C:32](B(O)O)=[CH:31][CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[K+].[K+].CC#N>CCOC(C)=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].O>[NH2:1][C@@H:2]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]3[N:15]([C:17]([C:32]4[C:27]([O:26][CH3:25])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:18][N:19]=3)[N:16]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 86696492HCID 86696492, compound

Product 1

HCID 86696491HCID 86696491, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 124 mg (0.20 mmol) of (S)-2-amino-1-(4-(3-bromoimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-4-methylpentan-1-one (di-TFA acid salt) in a microwaveable vial was added 51 mg (0.33 mmol) of the (2-methoxypyridin-3-yl)boronic acid, 110 mg (0.80 mmol) of K2CO3, 31 mg of PdCl2(dppf)2 3 mL of MeCN and 1.5 mL of water. This was microwaved for 0.5 hr at 140° C. It was then diluted with EtOAc, washed with brine, and the organic layer was dried over MgSO4 and concentrated. It was purified on by neutral PREP HPLC to obtain 51.6 mg (61%) of the desired product. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.98-1.10 (m, 6H) 1.60-1.84 (m, 3H) 3.48-3.60 (m, 2H) 3.62-3.81 (m, 5H) 3.94-4.02 (m, 1H) 4.05 (s, 3H) 4.48 (dd, J=9.47, 4.17 Hz, 1H) 7.13 (dd, J=7.45, 4.93 Hz, 1H) 7.27 (d, J=9.85 Hz, 1H) 7.88 (d, J=9.85 Hz, 1H) 8.01 (s, 1H) 8.17 (dd, J=5.05, 1.77 Hz, 1H) 8.51 (s, 2H) 8.66 (dd, J=7.58, 1.77 Hz, 1H).

Workup

  1. customThis was microwaved for 0.5 hr at 140° C
  2. washwashed with brine
  3. dry with materialthe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customIt was purified on by neutral PREP HPLC

Sources & evidence

ORD record
ord-acb3ac497ff64ccf91dc6933e300df50
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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