Diisopropylethylamine → 4-(((1R)-2-fluoro-1,2-dimethylpropyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507911Notes

Reaction equation

HRID 1507911 reaction equation
Cl[C:2]1[C:3]2[N:4]([CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:6][C:7]=1[C:8]([NH2:10])=[O:9].Cl.[F:15][C:16]([CH3:21])([CH3:20])[C@H:17]([NH2:19])[CH3:18].C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.CO>[F:15][C:16]([CH3:21])([CH3:20])[C@H:17]([NH:19][C:2]1[C:3]2[N:4]([CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:6][C:7]=1[C:8]([NH2:10])=[O:9])[CH3:18]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 679656194-Chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 86677913(2R)-3-fluoro-3-methylbutan-2-amine hydrochloride

Product 1

HCID 683494474-(((1R)-2-fluoro-1,2-dimethylpropyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 3, 50 mg, 0.26 mmol), (R)-2-Fluoro-1,2-dimethyl-propylamine hydrochloride salt (47 mg, 0.33 mmol, from step 3), and diisopropylethylamine (0.089 mL, 0.51 mmol) in NMP (0.5 mL) was heated to 100° C. for 1 hour in the CEM microwave. The mixture was cooled to rt, diluted with MeOH and purified by reverse-phase Prep HPLC (condition A). The fraction containing the major product was concentrated on the rotovap to remove the MeOH and the aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate. Sonication of the slurry followed by vacuum filtration and air drying in the funnel afforded 22 mg (33%) of a pale yellow solid as the title compound. HPLC (condition A): retention time=7.70 min. LCMS (condition B): m/z 265.2. 1H NMR (500 MHz, CD3OD) δ ppm 10.74 (1 H, br. s.), 8.16 (1 H, s), 7.41-7.80 (1 H, m), 7.01 (1 H, dd, J=4.72, 1.39 Hz), 6.72 (1 H, dd, J=4.58, 2.64 Hz), 4.28-4.64 (1 H, m), 1.46-1.55 (6 H, m), 1.44 (3 H, d).

Workup

  1. custompurified by reverse-phase Prep HPLC (condition A)
  2. additionThe fraction containing the major product
  3. concentrationwas concentrated on the rotovap
  4. customto remove the MeOH
  5. additionthe aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate
  6. customSonication of the slurry
  7. filtrationfollowed by vacuum filtration and air
  8. customdrying in the funnel

Sources & evidence

ORD record
ord-2fcbece341fd4f7f96e1dfab3fecd95c
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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