Benzaldehyde → HCID 11948472, compound

HRID 885695Notes

Reaction equation

HRID 885695 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][CH:18]([NH:22][CH2:23][C:24]3[CH:25]=[CH:26][C:27]4[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=4[CH:34]=3)[CH2:19]2)=[N:14]1.ClC(Cl)C.[CH:39](=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[BH4-].[Na+]>C(Cl)Cl.CN(C=O)C>[CH2:39]([N:22]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]2[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=2[CH:34]=1)[CH:18]1[CH2:17][CH2:16][C:15]2[C:20](=[CH:21][N:13]([C:6]3[C:5]4[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[N:4]=4)[N:9]=[CH:8][CH:7]=3)[N:14]=2)[CH2:19]1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 63651,1-DichloroethaneHCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 11948382HCID 11948382, compound

Product 1

HCID 11948472HCID 11948472, compoundYield 5.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 6-{[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one (30 mg, 0.06 mmol) and 4 Å molecular sieves (30 mg) was added dichloroethane (0.4 mL) and benzaldehyde (13 μL, 0.13 mmol). The solution was stirred for 1 h, after which NaB(OAc)3H (27 mg, 0.13 mmol) was added. After stirring overnight at RT, the reaction mixture was heated at 60° C. for 7 h. DMF (0.5 mL), NaBH4 (30 mg, 0.8 mmol) and CH2Cl2 (0.2 mL) were then added, and the reaction mixture was heated at 60° C. overnight. The mixture was diluted with satd. aq. NaHCO3 (10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The crude was purified directly by basic reverse phase HPLC to afford 2 mg (5%) of the title compound. MS (ESI): exact mass calculated for C32H30N6O2S, 562.22; m/z found, 563.5 [M+H]+.

Workup

  1. stirringAfter stirring overnight at RT
  2. temperaturethe reaction mixture was heated at 60° C. overnight
  3. additionThe mixture was diluted with satd
  4. extractionaq. NaHCO3 (10 mL) and extracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified directly by basic reverse phase HPLC

Sources & evidence

ORD record
ord-89b3a128880e4d90956f55b0b41cef03
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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