Diisopropylethylamine → (R)-4-(1-(1-fluorocyclopropyl)ethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507923Notes

Reaction equation

HRID 1507923 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]1([C@H:19]([NH2:21])[CH3:20])[CH2:18][CH2:17]1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.CO>[F:15][C:16]1([C@H:19]([NH:21][C:2]2[C:3]3[N:4]([CH:11]=[CH:12][CH:13]=3)[N:5]=[CH:6][C:7]=2[C:8]([NH2:10])=[O:9])[CH3:20])[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 679656194-Chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 68292141(R)-1-(1-fluorocyclopropyl)ethanamine hydrochloride

Product 1

HCID 68291814(R)-4-(1-(1-fluorocyclopropyl)ethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 15%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 3, 20 mg, 0.102 mmol), (R)-1-(1-fluorocyclopropyl)ethanamine hydrochloride (22 mg, 0.153 mmol), and diisopropylethylamine (0.054 mL, 0.31 mmol) in NMP (0.5 mL) was heated to 120° C. for 10 min 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 aqueous sodium bicarbonate. Sonication of the slurry followed by vacuum filtration and air drying in the funnel afforded 4 mg (14%) of a pale yellow solid as the title compound. HPLC (condition B): retention time=3.26 min. LCMS (condition B): MH+ m/z 263.2. 1H NMR (500 MHz, MeOD) δ ppm 8.17 (1 H, s), 7.64 (1 H, dd, J=2.64, 1.53 Hz), 7.27 (1 H, dd, J=4.44, 1.39 Hz), 6.74 (1 H, dd, J=4.44, 2.77 Hz), 5.07 (1 H, br. s.), 1.37-1.56 (3 H, m), 1.01-1.37 (4 H, m).

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 aqueous sodium bicarbonate
  6. customSonication of the slurry
  7. filtrationfollowed by vacuum filtration and air
  8. customdrying in the funnel

Sources & evidence

ORD record
ord-d9b3aa2e97df4f20a942b3f44bdce680
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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