Isobutyric Acid → HCID 68291294, compound
Reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16]([NH:17][C@@H:18]([CH:20]4[CH2:22][CH2:21]4)[CH3:19])=[C:15]([C:23]([NH2:25])=[O:24])[CH:14]=[N:13][N:12]3[CH:26]=2)[CH:6]=[CH:7][CH:8]=1.[C:27](O)(=[O:31])[CH:28]([CH3:30])[CH3:29].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH:20]1([C@H:18]([NH:17][C:16]2[C:11]3[N:12]([CH:26]=[C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][NH:1][C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])[CH:4]=4)[CH:10]=3)[N:13]=[CH:14][C:15]=2[C:23]([NH2:25])=[O:24])[CH3:19])[CH2:22][CH2:21]1Participants
Procedure
To a solution of 6-(3-(aminomethyl)phenyl)-4-(((1R)-1-cyclopropylethyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (Example 87, 15 mg, 0.043 mmol), isobutyric acid (3.99 μl, 0.043 mmol) and triethylamine (8.97 μl, 0.064 mmol) in DMF (0.5 mL) was added BOP (18.99 mg, 0.043 mmol) followed by stirring at rt for 30 minutes. The reaction mixture was purified by reverse-phase preparative HPLC (condition C) to yield the title compound (8.7 mg, 48%). HPLC (condition H): retention time=1.69 minute. LC/MS (M+H)+=420.3. 1H NMR (500 MHz, MeOD) δ ppm 8.04 (1 H, s), 7.82 (1 H, d, J=1.9 Hz), 7.48-7.52 (2 H, m), 7.33 (1 H, t, J=7.9 Hz), 7.15 (1 H, d, J=7.5 Hz), 7.06 (1 H, d, J=1.7 Hz), 4.41 (2 H, s), 4.04 (1 H, qd, J=6.4, 6.2 Hz), 2.48 (1 H, spt, J=6.9 Hz), 1.44 (3 H, d, J=6.4 Hz), 1.16 (6 H, d, J=6.9 Hz), 1.09-1.15 (1 H, m), 0.50-0.63 (2 H, m), 0.32-0.40 (2 H, m).
Workup
- customThe reaction mixture was purified by reverse-phase preparative HPLC (condition C)
Sources & evidence
- ORD record
- ord-a0ce22fc3d594e1bae1370d25dc9fc85
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221826B2
Reaction notes
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