HCID 68291410, compound → HCID 68291574, compound

HRID 877741Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:22][C@@H:14]4[CH2:15][N:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:17][C@@H:13]4[C@H:12]3[CH3:23])=[C:8]([C:24]([NH2:26])=[O:25])[CH:7]=[N:6][N:5]2[CH:27]=1.[Cu][C:29]#[N:30]>CN1CCCC1=O.C(OCC)(=O)C>[C:29]([C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:22][C@@H:14]4[CH2:15][N:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:17][C@@H:13]4[C@H:12]3[CH3:23])=[C:8]([C:24]([NH2:26])=[O:25])[CH:7]=[N:6][N:5]2[CH:27]=1)#[N:30]

Participants

Conditions

Temperature: 220 °C

Procedure

A mixture of 6-bromo-4-(((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 3 of Example 59 (70 mg, 0.153 mmol) and copper(I) cyanide (27.5 mg, 0.307 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was heated to 220° C. under microwave for 2 h. The resulting mixture was diluted with ethyl acetate (80 mL), washed with saturated NH4Cl, water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography, eluting with 60-100% ethyl acetate in hexanes, to give 6-cyano-4-(((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (35 mg, 56% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (d, J=1.8 Hz, 1H), 8.37 (s, 1H), 7.61 (d, J=1.5 Hz, 1H), 4.24-4.01 (m, 1H), 3.26-3.11 (m, 2H), 3.05 (m, 1H), 2.93 (s, 3H), 2.93-2.83 (m, 1H), 2.61-2.54 (m, 1H), 2.36-2.17 (m, 1H), 1.93-1.82 (m, 1H), 1.70-1.55 (m, 1H), 1.36-1.25 (m, 1H), 1.10-1.02 (m, 3H).

Workup

washwashed with saturated NH4Cl, water, brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluting with 60-100% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-f41bca52182d4da4ac6c416e69f518e4
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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