Potassium Carbonate → (R)-4-(1-cyclopropylethylamino)-6-(3-vinylphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507940Notes

Reaction equation

HRID 1507940 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]([CH:13]3[CH2:15][CH2:14]3)[CH3:12])=[C:8]([C:16]([NH2:18])=[O:17])[CH:7]=[N:6][N:5]2[CH:19]=1.[CH:20]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)=[CH2:21].C(=O)([O-])[O-].[K+].[K+]>COCCOC.CCOC(C)=O.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:13]1([C@H:11]([NH:10][C:9]2[C:4]3[N:5]([CH:19]=[C:2]([C:26]4[CH:25]=[CH:24][CH:23]=[C:22]([CH:20]=[CH2:21])[CH:27]=4)[CH:3]=3)[N:6]=[CH:7][C:8]=2[C:16]([NH2:18])=[O:17])[CH3:12])[CH2:15][CH2:14]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 43668863-Vinylphenylboronic Acid (contains varying amounts of Anhydride)HCID 68291753(R)-6-bromo-4-(1-cyclopropylethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide2×

Product 1

HCID 68291702(R)-4-(1-cyclopropylethylamino)-6-(3-vinylphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 27.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A degassed solution of (R)-6-bromo-4-(1-cyclopropylethylamino) pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 4, 25 mg, 0.077 mmol), 3-vinylphenyl boronic acid (34.3 mg, 0.232 mmol) and 2M aq. potassium carbonate (0.116 mL, 0.232 mmol) in DME (1 mL) was added Pd(Ph3P)4 (5.36 mg, 4.64 mmol) and the resulting reaction mixture was heated to 90° C. for 2 hrs. The reaction mixture was diluted with 10 mL of EtOAc which was washed with 5 mL of water and 5 mL of brine. The organic phase was concentrated to yield a crude product which was purified on a preparative silica gel TLC plate with hexanes/EtOAc (2/1) as the eluent to yield a product. After trituration in MeOH, the resulting solid obtained was dried to afford the title compound (7.25 mg, 26%). HPLC (condition G): retention time=3.833 min. LC/MS (M+H)+=m/z 347.2. 1H NMR (400 MHz, MeOD) δ ppm 8.12 (1 H, s), 7.93-7.95 (1 H, m), 7.72 (1 H, s), 7.55-7.60 (1 H, m), 7.34-7.37 (2 H, m), 7.22 (1 H, d, J=1.8 Hz), 6.81 (1 H, dd, J=17.8, 11.0 Hz), 5.86 (1 H, dd, J=17.7, 1.0 Hz), 5.27 (1 H, dd, J=11.0, 0.9 Hz), 4.09-4.17 (1 H, m), 1.46 (3 H, d, J=6.4 Hz), 1.11-1.21 (1 H, m), 0.53-0.64 (2 H, m), 0.37-0.47 (2 H, m).

Workup

  1. customthe resulting reaction mixture
  2. washwas washed with 5 mL of water and 5 mL of brine
  3. concentrationThe organic phase was concentrated
  4. customto yield a crude product which
  5. customwas purified on a preparative silica gel TLC plate with hexanes/EtOAc (2/1) as the eluent
  6. customto yield a product
  7. customwas dried

Sources & evidence

ORD record
ord-1b0b3dc07448461d9b9b092c2e81fd97
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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