Hydrazine → (R)-tert-butyl 4-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpiperidine-1-carboxylate

HRID 877746Notes

Reaction equation

HRID 877746 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[C:25]3[N:26]([CH:33]=[C:34]([C:36]([OH:38])=O)[CH:35]=3)[N:27]=[CH:28][C:29]=2[C:30](=[O:32])[NH2:31])[C:19]([CH3:40])([CH3:39])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].F[P-](F)(F)(F)(F)F.[N:48]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=[N:49]1.NN>CN(C)C=O.O>[C:30]([C:29]1[CH:28]=[N:27][N:26]2[CH:33]=[C:34]([C:36]([NH:48][NH2:49])=[O:38])[CH:35]=[C:25]2[C:24]=1[NH:23][C@@H:20]1[CH2:21][CH2:22][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:16])[CH2:18][C:19]1([CH3:39])[CH3:40])(=[O:32])[NH2:31]

Participants

7

Reactant 4

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68291940(R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid

Product 1

HCID 68291130(R)-tert-butyl 4-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpiperidine-1-carboxylateYield 76.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Hunig's base (0.752 mL, 4.30 mmol) was added to a mixture of (R)-4-((1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylic acid (619 mg, 1.435 mmol) and BOP (952 mg, 2.152 mmol) in N,N-dimethylformamide (4 mL). After 1 h at room temperature, hydrazine (0.225 mL, 7.17 mmol) was added. After additional 17 h at room temperature, the mixture was diluted with water to give a suspension. The precipitate was collected by filtration to give (R)-tert-butyl 4-((3-carbamoyl-6-(hydrazinecarbonyl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpiperidine-1-carboxylate (0.4863 g, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.08 (d, J=9.2 Hz, 1H), 9.64 (s, 1H), 8.27 (s, 1H), 8.03 (d, J=1.5 Hz, 1H), 7.31 (d, J=1.5 Hz, 1H), 4.13-4.00 (m, 1H), 3.87 (br. s., 1H), 3.60 (d, J=13.2 Hz, 1H), 3.17 (d, J=7.9 Hz, 1H), 2.92 (br. s., 1H), 1.90 (dd, J=13.4, 3.5 Hz, 1H), 1.62-1.48 (m, 1H), 1.46-1.35 (m, 9H), 0.98 (s, 3H), 0.92 (s, 3H); LC retention time: 3.295 min (analytical HPLC Method H).

Workup

  1. waitAfter additional 17 h at room temperature
  2. customto give a suspension
  3. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-8df17d23cc0c407c8fa3ccd35f42ca01
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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