Water → HCID 68291749, compound

HRID 1507990Notes

Reaction equation

HRID 1507990 reaction equation
[NH2:1][C:2](=[O:22])[C:3]([CH3:21])([CH3:20])[C@H:4]([NH:6][C:7]1[C:8]2[N:9]([CH:16]=[C:17](Br)[CH:18]=2)[N:10]=[CH:11][C:12]=1[C:13]([NH2:15])=[O:14])[CH3:5].O.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[NH2:1][C:2](=[O:22])[C:3]([CH3:21])([CH3:20])[C@H:4]([NH:6][C:7]1[C:8]2[N:9]([CH:16]=[C:17]([C:29]3[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[CH:18]=2)[N:10]=[CH:11][C:12]=1[C:13]([NH2:15])=[O:14])[CH3:5]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 68291929HCID 68291929, compound

Product 1

HCID 68291749HCID 68291749, compound

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

(R)-4-((4-amino-3,3-dimethyl-4-oxobutane-2-yl)amino)-6-bromopyrrolo[1,2-b]pyridazine-3-carboxamide (50 mg, 0.136 mmol) was taken in a sealed tube contained in acetonitrile (8 mL) and water (0.8 ml) mixture was added 4-methoxyphenylboronic acid (37.1 mg, 0.204 mmol), sodium carbonate (43.2 mg, 0.407 mmol). The reaction was degassed for 10 min. Next, PdCl2(TPP)2 (14.90 mg, 0.020 mmol) was added and the reaction mixture was heated to 100° C. and stirred for 30 min. After completion of reaction, it was then quenched with water (30 ml) and extracted into EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and solvent was removed under vacuum. Crude product was purified by prep HPLC purification to get desired product as an off white solid (16 mg, 29.8% yield). 1HNMR (400 MHz, DMSO) δ ppm: 1.16-1.19 (d, J=12 Hz, 6H), 1.23-1.24 (d, J=4.0 Hz, 3H), 3.79 (s, 3H), 4.69-4.73 (t, J=16 Hz, 1H), 6.95-7.01 (m, 3H), 7.214-7.263 (d, J=19.6 Hz, 4H), 7.67-7.70 (d, J=12 Hz, 2H), 8.08 (s, 1H), 8.198 (s, 1H), 10.827-10.851 (d, J=9.6 Hz, 1H). column: Purospherstar RP-18 (4×55) mm, 3 μm. Buffer: 20 mM NH4OAc in Water, Mobile Phase: A-Buffer+ACN (90+10), B-Buffer+ACN (10+90); Flow: 2.5 mL/min, Retention Time: 1.520 min, Purity: 99.46%. HPLC: Column: SUNFIRE C18 (4.6×150) mm, 3.5 micron Buffer: 0.05% TFA in water pH 2.5 Mobile phase: A: Buffer:Acetonitrile (95:5) B: Acetonitrile:buffer (95:5) Flow: 1.0 mL/min Retention Time: 8.269 min Enantioselectivity: 98.66%.

Workup

  1. customThe reaction was degassed for 10 min
  2. customAfter completion of reaction, it
  3. customwas then quenched with water (30 ml)
  4. extractionextracted into EtOAc (3×20 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4 and solvent
  6. customwas removed under vacuum
  7. customCrude product was purified by prep HPLC purification

Sources & evidence

ORD record
ord-857f2dedf8504ec39f86ed33e654b76a
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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