p-Toluenesulfonic acid monohydrate → HCID 178493403, compound

HRID 591690Notes

Reaction equation

HRID 591690 reaction equation
O1CCCCC1[O:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:18]=O)[CH:16]=2)[NH:11][N:10]=1.[NH2:20][C:21]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[C:26]([O:32][CH3:33])[C:22]=1[C:23]([NH2:25])=[O:24].OS([O-])=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[OH:7][CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:18]3[NH:25][C:23](=[O:24])[C:22]4[C:21](=[CH:29][C:28]([O:30][CH3:31])=[CH:27][C:26]=4[O:32][CH3:33])[N:20]=3)[CH:16]=2)[NH:11][N:10]=1

Participants

6

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 178519378HCID 178519378, compound

Product 1

HCID 178493403HCID 178493403, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(tetrahydro-pyran-2-yloxymethyl)-1H-indazole-5-carbaldehyde (0.32 g, 1.23 mmol) and 2-amino-4,6-dimethoxy-benzamide (0.24 g, 1.23 mmol) in N,N-dimethylacetamide (10 mL) were added NaHSO3 (58.5 wt %, 0.27 g, 1.48 mmol) and p-toluenesulfonic acid monohydrate (0.05 g, 0.25 mmol); the reaction mixture was heated at 120° C. for 16 hours, then cooled to room temperature. Solvent was removed under reduced pressure. The residue was diluted with water (100 mL). The separated solid was filtered and washed with water and dried under vacuum. The residue was purified by the Simpliflash system (0-5% methanol in CH2Cl2 as eluent) to give the title compound as an off-white solid. Yield: 30 mg (7%). MP 264-266° C. 1H NMR (400 MHz, CD3OD): δ 8.60 (s, 1H), 8.10 (d, J=8.98 Hz, 1H), 7.65 (d, J=8.98 Hz, 1H), 6.85 (d, J=1.95 Hz, 1H), 6.55 (d, J=1.95 Hz, 1H), 5.05 (s, 2H), 3.96 (s, 6H).

Workup

  1. temperaturecooled to room temperature
  2. customSolvent was removed under reduced pressure
  3. additionThe residue was diluted with water (100 mL)
  4. filtrationThe separated solid was filtered
  5. washwashed with water
  6. customdried under vacuum
  7. customThe residue was purified by the Simpliflash system (0-5% methanol in CH2Cl2 as eluent)

Sources & evidence

ORD record
ord-097decc652d742dd894d9471e19c043d
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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