Methoxyacetic Acid → (3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

HRID 877781Notes

Reaction equation

HRID 877781 reaction equation
[NH2:1][CH2:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[C:16]([NH:17][C@H:18]4[C@@H:22]([CH2:23][CH3:24])[CH2:21][N:20]([C:25]([O:27][CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[O:26])[CH2:19]4)=[C:15]([C:35](=[O:37])[NH2:36])[CH:14]=[N:13][N:12]3[CH:38]=2)=[CH:5][CH:4]=1.[CH3:39][O:40][CH2:41][C:42](O)=[O:43].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:35]([C:15]1[CH:14]=[N:13][N:12]2[CH:38]=[C:9]([C:6]3[CH:7]=[N:8][C:3]([CH2:2][NH:1][C:42](=[O:43])[CH2:41][O:40][CH3:39])=[CH:4][CH:5]=3)[CH:10]=[C:11]2[C:16]=1[NH:17][C@H:18]1[C@@H:22]([CH2:23][CH3:24])[CH2:21][N:20]([C:25]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[O:26])[CH2:19]1)(=[O:37])[NH2:36]

Participants

6

Reactant 4

HCID 12251Methoxyacetic AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68350398(3S,4S)-benzyl 3-((6-(6-(aminomethyl)pyridin-3-yl)-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

Product 1

HCID 68350395(3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylateYield 67.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (3S,4S)-benzyl 3-((6-(6-(aminomethyl)pyridin-3-yl)-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (29 mg, 0.056 mmol), 2-methoxyacetic acid (9.56 μl, 0.124 mmol), BOP (54.9 mg, 0.124 mmol) and diisopropylethylamine (0.039 mL, 0.226 mmol) in DMF (0.5 mL) was stirred at rt overnight. The reaction mixture was partitioned between EtOAc (20 ml) and 10% LiCl solution (20 ml). The organic layer was washed with 10% LiCl solution (2×20 ml) and brine (20 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to afford (3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (22 mg, 0.038 mmol, 66.5% yield) as a yellow semisolid. The material will be used as is in the next step. MS (ES+) m/z: 586.22 (M+H); LC retention time: 2.370 min (analytical HPLC Method O).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (20 ml) and 10% LiCl solution (20 ml)
  2. washThe organic layer was washed with 10% LiCl solution (2×20 ml) and brine (20 ml)
  3. customAfter drying
  4. filtration(MgSO4) and filtration
  5. concentrationthe organic layer was concentrated

Sources & evidence

ORD record
ord-88bbcb2288b4445fadf62c934025ad9b
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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