Ethyl Acetate → (S)-tert-butyl 3-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate

HRID 877725Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)=[C:8]([C:24](=[O:26])[NH2:25])[CH:7]=[N:6][N:5]2[CH:27]=1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:24]([C:8]1[CH:7]=[N:6][N:5]2[CH:27]=[C:2]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:3]=[C:4]2[C:9]=1[NH:10][C@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)(=[O:26])[NH2:25]

Participants

Conditions

Temperature: 130 °C

Procedure

A solution of (S)-tert-butyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)piperidine-1-carboxylate (75 mg, 0.17 mmol), phenylboronic acid (31.3 mg, 0.26 mmol), and PdCl2(dppf) 6.3 mg, (0.009 mmol) in DMF (1.5 mL) was added aq. K3PO4 (2M, 0.26 mL) then heated at 130° C. for 25 min. The mixture was poured into ethyl acetate (with 20% heptane) and washed with water then sat. aq. NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified via column chromatography (50-75% ethyl acetate in heptane) to afford the title compound (63 mg, 85% yield). LCMS 436.16 (M+H)+; HPLC (conditions L): retention time=4.02 min.

Workup

washwashed with water
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified via column chromatography (50-75% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-0e2edb18cfec491eaf24570dc83d7091
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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