Diisopropylethylamine → ethyl 4-(((3S,4S)-1-((benzyloxy)carbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

HRID 877793Notes

Reaction equation

HRID 877793 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:12]=[C:6]2[C:5]=1Cl)(=[O:3])[NH2:2].[NH2:19][C@H:20]1[C@@H:24]([CH3:25])[CH2:23][N:22]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:21]1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[CH2:29]([O:28][C:26]([N:22]1[CH2:23][C@H:24]([CH3:25])[C@H:20]([NH:19][C:5]2[C:6]3[N:7]([CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:12]=3)[N:8]=[CH:9][C:4]=2[C:1](=[O:3])[NH2:2])[CH2:21]1)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68290691Ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate2×HCID 68350278(3S,4S)-benzyl 3-amino-4-methylpyrrolidine-1-carboxylate2×

Product 1

HCID 68291339ethyl 4-(((3S,4S)-1-((benzyloxy)carbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (Intermediate 1, 375 mg, 1.401 mmol), (3S,4S)-benzyl 3-amino-4-methylpyrrolidine-1-carboxylate (Intermediate 5, 361 mg, 1.541 mmol) and diisopropylethylamine (0.734 mL, 4.20 mmol) in DMA (5 mL) was heated to 100° C. for 3 hr. After cooling, the volatiles were removed in vacuo and the residue was triturated with water. Filtration and drying afforded a tan solid that was rinsed with hexane and redried to afford ethyl 4-(((3S,4S)-1-((benzyloxy)carbonyl)-4-methylpyrrolidin-3-yl)amino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate (650 mg, 1.396 mmol, 100% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 11.29 (d, J=7.3 Hz, 1H), 8.34 (s, 1H), 8.13 (d, J=2.4 Hz, 1H), 7.50-7.06 (m, 7H), 5.15-4.96 (m, 2H), 4.81 (d, J=4.8 Hz, 1H), 4.35-4.20 (m, 2H), 3.85-3.63 (m, 2H), 3.45 (dd, J=10.9, 3.4 Hz, 1H), 3.09 (dt, J=16.1, 10.2 Hz, 1H), 2.72-2.58 (m, 1H), 1.34-1.27 (m, 3H), 1.07 (d, J=6.8 Hz, 3H). MS (ES+) m/z: 466.3 (M+H); LC retention time: 3.095 min (analytical HPLC Method O).

Workup

  1. temperatureAfter cooling
  2. customthe volatiles were removed in vacuo
  3. customthe residue was triturated with water
  4. filtrationFiltration
  5. customdrying
  6. customafforded a tan solid
  7. washthat was rinsed with hexane
  8. customredried

Sources & evidence

ORD record
ord-d5138a309bb84ab1b820943697e37088
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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