Potassium Carbonate → 4-(((1R)-1-cyclopropylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507918Notes

Reaction equation

HRID 1507918 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.[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH:13]1([C@H:11]([NH:10][C:9]2[C:4]3[N:5]([CH:19]=[C:2]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=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

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 68291753(R)-6-bromo-4-(1-cyclopropylethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide2×

Product 1

HCID 682917434-(((1R)-1-cyclopropylethyl)amino)-6-phenylpyrrolo[1,2-b]pyridazine-3-carboxamideYield 49.3%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A degassed solution of (R)-6-bromo-4-(1-cyclopropylethylamino) pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 4, 20 mg, 0.062 mmol), phenylboronic acid (22.64 mg, 0.186 mmol), potassium carbonate (0.077 mL, 0.155 mmol, 2M) and palladium tetrakis(triphenylphosphine) (4.29 mg, 3.71 μmol) in DME (1 mL) was heated to 90° C. for 1 hr. The reaction mixture was concentrated and redissolved in 1 mL of MeOH, and purified by reverse-phase preparative HPLC (condition C) to yield the title compound (9.8 mg, 48%). HPLC (condition I): retention time=2.49 min. LC/MS (M+H)+=321.1. 1H NMR (500 MHz, MeOD) δ ppm 8.04 (1 H, s), 7.82 (1 H, d, J=1.7 Hz), 7.61 (1 H, d, J=1.1 Hz), 7.59 (1 H, d, J=0.8 Hz), 7.56 (1 H, s), 7.37 (2 H, t, J=7.8 Hz), 7.21-7.26 (1 H, m), 4.05 (1 H, quin, J=6.4 Hz), 1.44 (3 H, d, J=6.4 Hz), 1.08-1.17 (1 H, m), 0.52-0.62 (2 H, m), 0.35-0.41 (2 H, m).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionredissolved in 1 mL of MeOH
  3. custompurified by reverse-phase preparative HPLC (condition C)

Sources & evidence

ORD record
ord-799e745315b94ce999b6ccd7d3385974
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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