HCID 68292387, compound → HCID 66547151, compound

HRID 1507914Notes

Reaction equation

HRID 1507914 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16]([NH:17][C@@H:18]([C:20]([F:23])([CH3:22])[CH3:21])[CH3:19])=[C:15]([C:24]([NH2:26])=[O:25])[CH:14]=[N:13][N:12]3[CH:27]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]>C(O)C.[Ni]>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16]([NH:17][C@H:18]([CH3:19])[C:20]([F:23])([CH3:22])[CH3:21])=[C:15]([C:24]([NH2:26])=[O:25])[CH:14]=[N:13][N:12]3[CH:27]=2)[CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 1

HCID 68292387HCID 68292387, compound

Product 1

HCID 66547151HCID 66547151, compoundYield 97.1%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

A suspension of (R)-6-(3-cyanophenyl)-4-(3-fluoro-3-methylbutan-2-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (Example 53, 110 mg, 0.301 mmol) and Raney 3201 Nickel (17.67 mg, 0.301 mmol) in ethanol (5 mL) was bubbled with ammonia gas for 3 minutes then stirred under a balloon of hydrogen for 6 hrs. The reaction mixture was filtered and concentrated to yield the title compound (108 mg, 97%). HPLC (condition G): retention time=2.330 minute. LC/MS (M+H)+=370.3. 1H NMR (400 MHz, MeOD) δ ppm 8.18 (1 H, s), 8.01 (1 H, d, J=1.8 Hz), 7.78-7.84 (2 H, m), 7.50 (1 H, t, J=8.0 Hz), 7.35 (1 H, d, J=7.7 Hz), 7.28 (1 H, d, J=1.8 Hz), 4.45-4.61 (1 H, m), 4.18 (2 H, s), 1.52 (3 H, d, J=2.4 Hz), 1.45-1.49 (6 H, m).

Workup

  1. customwas bubbled with ammonia gas for 3 minutes
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-4505b5656ff14a8fa1a881d4466e236a
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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