Diisopropylethylamine → (R)-6-bromo-4-(1-(1-fluorocyclopropyl)ethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507924Notes

Reaction equation

HRID 1507924 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.Cl.[F:16][C:17]1([C@H:20]([NH2:22])[CH3:21])[CH2:19][CH2:18]1.FC1([C@H](NC2C3N(C=CC=3)N=CC=2C(N)=O)C)CC1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:22][C@@H:20]([C:17]3([F:16])[CH2:19][CH2:18]3)[CH3:21])=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 68291814(R)-4-(1-(1-fluorocyclopropyl)ethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamideHCID 68292141(R)-1-(1-fluorocyclopropyl)ethanamine hydrochloride

Product 1

HCID 68291779(R)-6-bromo-4-(1-(1-fluorocyclopropyl)ethylamino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 16.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 5, 200 mg, 0.73 mmol), (R)-1-(1-fluorocyclopropyl)ethanamine hydrochloride (153 mg, 1.1 mmol, from step 4 of Intermediate 5), and diisopropylethylamine (0.38 mL, 2.2 mmol) in NMP (0.7 mL) was heated to 150° 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 aqueous sodium bicarbonate. Sonication of the slurry followed by vacuum filtration and air drying in the funnel afforded 40 mg (16%) of a pale yellow solid as the title compound. HPLC (condition B): retention time=3.75 min. LCMS (condition B): MH+ m/z 342.7.

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-83f8c46986774e1f87a29b4cc8c3c2d5
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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