Formaldehyde → 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(1-methylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamide

HRID 63543Notes

Reaction equation

HRID 63543 reaction equation
[NH:1]1[CH2:4][CH:3]([CH2:5][CH2:6][N:7]([S:31]([CH3:34])(=[O:33])=[O:32])[C:8]2[C:9]([CH:28]3[CH2:30][CH2:29]3)=[CH:10][C:11]3[C:15]([CH:16]=2)=[N:14][N:13]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[C:12]=3[C:24]([NH:26][CH3:27])=[O:25])[CH2:2]1.[CH2:35]=O.[BH4-].[Na+].O>CO>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([N:13]2[C:12]([C:24]([NH:26][CH3:27])=[O:25])=[C:11]3[C:15]([CH:16]=[C:8]([N:7]([CH2:6][CH2:5][CH:3]4[CH2:4][N:1]([CH3:35])[CH2:2]4)[S:31]([CH3:34])(=[O:33])=[O:32])[C:9]([CH:28]4[CH2:29][CH2:30]4)=[CH:10]3)=[N:14]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 4311764Sodium borohydrideHCID 717690346-{[2-(Azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide

Product 1

HCID 717686102-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-{[2-(1-methylazetidin-3-yl)ethyl](methylsulfonyl)amino}-2H-indazole-3-carboxamideYield 124%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of Compound (6) (27 mg, 0.05 mmol) in MeOH (2 mL) was added, simultaneously, paraformaldehyde (30 mg) and sodium borohydride (30 mg). After 16 h at ambient temperature water (25 ml) was added and the aqueous layer was extracted into EtOAc (3×30 mL). The combined organics were washed with brine (25 mL), dried (MgSO4) and concentrated in vacuo to give a colourless oil (32 mg). The crude material was purified by reverse phase preparative LCMS: Acetonitrile/water (0.1% formic acid) to give Compound (7) (7.70 mg, 30%). ESI-MS m/z calculated for [M+H]+: 516.2. found: 516.1. 1H NMR (400 MHz, CD3CN, formate salt) δ 8.30 (s, 1H), 7.79 (s, 1H), 7.62-7.49 (m, 4H), 7.35 (s, 1H), 7.22 (br s, 1H), 3.84-3.70 (m, 2H), 3.70-3.56 (m, 2H), 3.38 (dd, J=16.0, 7.5 Hz, 2H), 3.07 (s, 3H), 2.89 (d, J=4.8 Hz, 3H), 2.75 (dt, J=15.4, 7.8 Hz, 1H), 2.51 (s, 3H), 2.35 (ddd, J=13.6, 8.1, 5.6 Hz, 1H), 1.87 (ddd, J=17.6, 11.0, 5.2 Hz, 2H), 1.11-0.98 (m, 3H), 0.65-0.57 (m, 1H).

Workup

  1. extractionthe aqueous layer was extracted into EtOAc (3×30 mL)
  2. washThe combined organics were washed with brine (25 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7ac2aebaae1242eab74571a0d078b44b
Source dataset
uspto-grants-2016_09
Patent number
US09447080B2

Reaction notes

Loading…