HCID 86707702, compound → HCID 68291545, compound

HRID 1408943Notes

Reaction equation

CS(O[C@H:6]1[CH2:10][CH2:9][C@@H:8]([NH:11][C:12]2[C:13]3[N:14]([CH:21]=[CH:22][CH:23]=3)[N:15]=[CH:16][C:17]=2[C:18](=[O:20])[NH2:19])[C:7]1([CH3:25])[CH3:24])(=O)=O>CN(C)C=O>[CH3:24][C:7]1([CH3:25])[CH:6]=[CH:10][CH2:9][CH:8]1[NH:11][C:12]1[C:13]2[N:14]([CH:21]=[CH:22][CH:23]=2)[N:15]=[CH:16][C:17]=1[C:18]([NH2:19])=[O:20]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of crude cis-3-(3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-2,2-dimethylcyclopentyl methanesulfonate (from Step 1), 1,8-diazabiclo[5,4,0]undec-7-ene (0.235 mL, 1.561 mmol) and N,N-dimethylformamide (2 mL) was stirred at 130° C. for 2 h, cooled to room temperature and quenched with saturated sodium bicarbonate (3 mL). Following addition of ethyl acetate (80 mL), the mixture was washed with water, brine, dried (MgSO4), filtered and concentrated. Silica gel chromatography, eluting with 20 to 100% ethyl acetate in hexanes, gave the title compound (40 mg, 47% yield for 2 steps). 1H NMR (400 MHz, methanol-d4) δ ppm 10.70 (1 H, d, J=8.58 Hz), 7.87-8.20 (1 H, m), 7.57 (1 H, dd, J=2.64, 1.54 Hz), 6.99 (1 H, dd, J=4.73, 1.43 Hz), 6.67 (1 H, dd, J=4.62, 2.86 Hz), 5.60-5.87 (2 H, m), 4.47-4.64 (1 H, m), 2.78-3.15 (1 H, m), 2.23-2.51 (1 H, m), 1.01-1.24 (6 H, m); MS (ES+) m/z:=271.2 (M+H).

Workup

temperaturecooled to room temperature
customquenched with saturated sodium bicarbonate (3 mL)
additionaddition of ethyl acetate (80 mL)
washthe mixture was washed with water, brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
washSilica gel chromatography, eluting with 20 to 100% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-6bad3abb047e4fdc8c6ea736d2963faa
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921368B2

Reaction notes

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