Ethyl Acetate → tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate

HRID 1408985

Reaction equation

HRID 1408985 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]1([CH3:32])[CH2:13][CH2:12][C@@H:11]([NH:14][C:15]2[C:16]3[N:17]([CH:24]=[C:25]([C:27]([OH:29])=O)[CH:26]=3)[N:18]=[CH:19][C:20]=2[C:21](=[O:23])[NH2:22])[C:10]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.[N:40]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=[N:41]1.NN.CCOC(C)=O>CN(C=O)C>[C:21]([C:20]1[CH:19]=[N:18][N:17]2[CH:24]=[C:25]([C:27]([NH:40][NH2:41])=[O:29])[CH:26]=[C:16]2[C:15]=1[NH:14][C@@H:11]1[CH2:12][CH2:13][C@@:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:32])[C:10]1([CH3:31])[CH3:30])(=[O:23])[NH2:22]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9321HydrazineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 867077164-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid

Product 1

HCID 86707718tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamateYield 106.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(((1R,3S)-3-((tert-butoxycarbonyl)amino)-2,2,3-trimethylcyclopentyl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid (3.0 g, 6.73 mmol), BOP (3.57 g, 8.08 mmol) and hydrazine (1.057 mL, 33.7 mmol) in DMF (25 mL) was stirred for 30 minutes, and then the reaction mixture was added 350 mL of EtOAc which was washed with 10% LiCl solution (2×100 mL), 100 mL of brine and dried over Na2SO4. Filtration and concentration gave the desired tert-butyl ((1S,3R)-3-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-1,2,2-trimethylcyclopentyl)carbamate (3.29 g, 99% yield). HPLC retention time=2.457 min., LC/MS (M+H)+=460.4.

Workup

  1. washwas washed with 10% LiCl solution (2×100 mL), 100 mL of brine
  2. dry with materialdried over Na2SO4
  3. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-440cc2c16bd2465ba941177ae109fee2
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Linked notes

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