Pyridine → HCID 71768587, compound

HRID 63544Notes

Reaction equation

HRID 63544 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.[C:35](OC(=O)C)(=[O:37])[CH3:36].N1C=CC=CC=1>C(Cl)Cl>[C:35]([N: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[CH2:29][CH2:30]3)=[CH:10][C:11]3[C:15]([CH:16]=2)=[N:14][N:13]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[C:12]=3[C:24]([NH:26][CH3:27])=[O:25])[CH2:2]1)(=[O:37])[CH3:36]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 717690346-{[2-(Azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide

Product 1

HCID 71768587HCID 71768587, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Compound (6) (8 mg, 0.02 mmol) in DCM (2.0 mL) was added acetic anhydride (0.1 mL) and pyridine (0.1 mL) and the mixture was stirred at ambient temperature for 16 h. The reaction mixture was then concentrated in vacuo and the residue partitioned between EtOAc (25 mL) and water (15 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organics were washed with brine (15 mL), dried (MgSO4) and concentrated in vacuo (32 mg). The crude material was purified by reverse phase preparative LCMS: Acetonitrile/water (0.1% formic acid) to give Compound (8) (2.14 mg, 20%). ESI-MS m/z calculated for [M+H]+: 544.2. found: 544.1. 1H NMR (400 MHz, CD3CN) δ 7.85 (s, 1H), 7.63-7.54 (m, 4H), 7.40 (s, 1H), 7.05 (br s, 1H), 4.21-4.14 (m, 1H), 3.93 (td, J=8.9, 3.2 Hz, 1H), 3.76-3.67 (m, 3H), 3.49-3.43 (m, 1H), 3.11 (d, J=1.0 Hz, 3H), 2.93 (d, J=4.8 Hz, 3H), 2.77-2.64 (m, 1H), 2.46-2.36 (m, 1H), 1.95-1.81 (m, 2H), 1.73 (d, J=2.4 Hz, 3H), 1.14-1.02 (m, 3H), 0.69-0.58 (m, 1H).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customthe residue partitioned between EtOAc (25 mL) and water (15 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  5. washThe combined organics were washed with brine (15 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo (32 mg)
  8. customThe crude material was purified by reverse phase preparative LCMS

Sources & evidence

ORD record
ord-fd37fd7e05344c9f86eb42b4f4ab2899
Source dataset
uspto-grants-2016_09
Patent number
US09447080B2

Reaction notes

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