Isobutylamine → 5-cyclopropyl-6-[ethyl(methylsulfonyl)amino]-2-[6-(isobutylamino)-3-pyridyl]-N-methyl-2H-indazole-3-carboxamide

HRID 1037571Notes

Reaction equation

HRID 1037571 reaction equation
[CH:1]1([C:4]2[C:12]([N:13]([CH2:18][CH2:19]CN3C(=O)C4C(=CC=CC=4)C3=O)[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][C:10]3[C:6](=[C:7]([C:46]([NH:48][CH3:49])=[O:47])[N:8]([C:32]4C=C[C:35]([NH:38]C5C=CC(F)=CC=5)=[CH:34][CH:33]=4)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1.[CH2:50]([NH2:54])[CH:51]([CH3:53])[CH3:52].O1CCOC[CH2:56]1>>[CH:1]1([C:4]2[C:12]([N:13]([CH2:18][CH3:19])[S:14]([CH3:17])(=[O:15])=[O:16])=[CH:11][C:10]3[C:6](=[C:7]([C:46]([NH:48][CH3:49])=[O:47])[N:8]([C:32]4[CH:56]=[N:38][C:35]([NH:54][CH2:50][CH:51]([CH3:53])[CH3:52])=[CH:34][CH:33]=4)[N:9]=3)[CH:5]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 6558Isobutylamine2×HCID 312751,4-DioxaneHCID 69248953HCID 69248953, compound

Product 1

HCID 677753885-cyclopropyl-6-[ethyl(methylsulfonyl)amino]-2-[6-(isobutylamino)-3-pyridyl]-N-methyl-2H-indazole-3-carboxamide

Conditions

Temperature
70 °C

Procedure

To a solution of compound (iii) (4.7 mg, 0.0084 mmol) and isobutylamine (0.1 mL) in 1,4-dioxane (0.3 mL) was heated to 40° C. and stirred for 45 min. More isobutylamine (100 μL) was added and the mixture was heated at 70° C. for 1.5 h. The mixture was cooled to RT and concentrated under reduced pressure. The residue was purified by preparative LCMS (5-30-50-100% acetonitrile in 0.1% aqueous formic acid) to give Compound (110) as a white solid. ESI-MS m/z calculated for [M+H]+: 485.2; found: 485.2; 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=1.9 Hz, 1H), 7.86 (dd, J=9.3, 2.1 Hz, 1H), 7.68 (s, 1H), 7.32 (s, 1H), 6.82 (brs, 1H), 6.69 (d, J=9.3 Hz, 1H), 6.17 (brs, 1H), 3.88-3.71 (m, 2H), 3.24-3.13 (m, 2H), 3.08 (s, 3H), 3.03 (d, J=4.9 Hz, 3H), 2.39 (ddd, J=13.9, 8.4, 5.5 Hz, 1H), 2.04-1.89 (m, 1H), 1.23 (t, J=7.1 Hz, 3H), 1.11-0.97 (m, 9H), 0.66-0.45 (m, 1H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by preparative LCMS (5-30-50-100% acetonitrile in 0.1% aqueous formic acid)

Sources & evidence

ORD record
ord-a1898e89bef3419e93217f00c30d346e
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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