Water → (R)-ethyl 3-carbamoyl-4-((1-cyclopropylethyl)amino)pyrrolo[1,2-b]pyridazine-6-carboxylate

HRID 1507929Notes

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].CC[N:21]([CH:25]([CH3:27])[CH3:26])C(C)C.O.CN1C(=O)C[CH2:32][CH2:31]1>>[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]=1[NH:21][C@@H:25]([CH:26]1[CH2:32][CH2:31]1)[CH3:27])(=[O:3])[NH2:2]

Participants

Reactant 4

HCID 962Water

HCID 13387N-methyl-2-pyrrolidone

HCID 81531Diisopropylethylamine

HCID 68290691Ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate

Product 1

HCID 68349350(R)-ethyl 3-carbamoyl-4-((1-cyclopropylethyl)amino)pyrrolo[1,2-b]pyridazine-6-carboxylateYield 86%

Procedure

A solution of ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (1.0 g, 3.74 mmol), (R)-1-cyclopropylethanamine, HCl (0.500 g, 4.11 mmol) and DIPEA (1.468 mL, 8.41 mmol) in NMP (Volume: 5 mL) was heated to 100° C. for 4 hr. The reaction mixture was added 30 mL of water and stirred for 10 minutes. The solid was collected as the desired product (1.1 g, 86% yield). 1H NMR (400 MHz, CD3OD) δ 8.22 (s, 1H), 8.03 (d, J=1.8 Hz, 1H), 7.34 (d, J=1.8 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.08-3.96 (m, 1H), 1.46 (d, J=6.4 Hz, 3H), 1.41 (t, J=7.2 Hz, 3H), 1.22-1.12 (m, 1H), 0.62 (dd, J=10.9, 8.3 Hz, 2H), 0.43-0.36 (m, 2H). MS (ES+) m/z: 317.1 (M+H); HPLC: 92.6%, retention time: 3.080 min (analytical HPLC Method Q).

Sources & evidence

ORD record: ord-36d831ed03674ceab0bc140b4770b1b5
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221826B2

Reaction notes

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