Pyridine → HCID 56963343, compound

HRID 1037553Notes

Reaction equation

HRID 1037553 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([CH2:29][CH2:30]CO)[S:25]([CH3:28])(=[O:27])=[O:26])[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.[N:33]1C=CC=C[CH:34]=1.[CH:39]1([C:43](Cl)=[O:44])[CH2:42][CH2:41][CH2:40]1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([CH2:29][CH2:30][CH2:34][NH:33][C:43]([CH:39]4[CH2:42][CH2:41][CH2:40]4)=[O:44])[S:25]([CH3:28])(=[O:26])=[O:27])[C:13]([CH:21]4[CH2:22][CH2:23]4)=[CH:14]3)=[N:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 78705Cyclobutanecarbonyl chloride2×HCID 569627692-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamide

Product 1

HCID 56963343HCID 56963343, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-[3-aminopropyl(methylsulfonyl)amino]-2-(4-bromophenyl)-5-cyclopropyl-N-methyl-indazole-3-carboxamide (i) (5 mg, 0.01 mmol) in DCM (0.5 mL) at 0° C. was added pyridine (50 μL) followed by cyclobutanecarbonyl chloride (3 μL, 0.026 mmol). The mixture was then stirred at RT for 16 h. More pyridine (20 μL) and cyclobutylcarbonyl chloride (10 μL) were added and the mixture was left to stir for another 5 h. The solvent was then evaporated under reduced pressure. The residue was taken up in EtOAc (2 mL), washed with saturated aqueous sodium bicarbonate solution (1 mL), dried (MgSO4) and concentrated in vacuo. The crude material was purified by preparative LCMS (5-40-70-100% ACN in 0.1% aqueous formic acid) to afford Compound (62) as a white solid (2.5 mg, 43%). ESI-MS m/z calculated for [M+H]+: 602.1/604.1; found: 601.9/603.9; 1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.71-7.60 (m, 2H), 7.50-7.41 (m, 2H), 7.36 (s, 1H), 5.82 (t, J=6.0 Hz, 2H), 3.92-3.65 (m, 2H), 3.55-3.26 (m, 2H), 3.04 (d, J=11.1 Hz, 3H), 3.02-2.90 (m, 4H), 2.44-2.30 (m, 1H), 2.30-2.07 (m, 4H), 2.03-1.81 (m, 2H), 1.77 (p, J=6.6 Hz, 2H), 1.17-0.94 (m, 3H), 0.72-0.52 (m, 1H).

Workup

  1. waitthe mixture was left
  2. stirringto stir for another 5 h
  3. customThe solvent was then evaporated under reduced pressure
  4. washwashed with saturated aqueous sodium bicarbonate solution (1 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by preparative LCMS (5-40-70-100% ACN in 0.1% aqueous formic acid)

Sources & evidence

ORD record
ord-424a35b31c2240de81342df2165e457b
Source dataset
uspto-grants-2013_10
Patent number
US08546389B2

Reaction notes

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