Diisopropylethylamine → HCID 9958698, compound

HRID 1611099Notes

Reaction equation

HRID 1611099 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:10]=O)[CH:8]=2)[CH:3]=[CH:2]1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([C:22]2[CH:23]=[N:24][C:25]([S:28][CH2:29][C:30]([NH:32][CH2:33][CH:34]3[CH2:39][CH2:38][CH2:37][NH:36][CH2:35]3)=[O:31])=[N:26][CH:27]=2)[CH:17]=[CH:18][C:19]=1[O:20][CH3:21].C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CO>[CH3:12][O:13][C:14]1[CH:15]=[C:16]([C:22]2[CH:23]=[N:24][C:25]([S:28][CH2:29][C:30]([NH:32][CH2:33][CH:34]3[CH2:39][CH2:38][CH2:37][N:36]([CH2:10][C:7]4[CH:8]=[C:9]5[C:4]([CH:3]=[CH:2][NH:1]5)=[CH:5][CH:6]=4)[CH2:35]3)=[O:31])=[N:26][CH:27]=2)[CH:17]=[CH:18][C:19]=1[O:20][CH3:21]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27734351H-Indole-6-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 11711108HCID 11711108, compound

Product 1

HCID 9958698HCID 9958698, compoundYield 64.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Procedure

1H-indole-6-carbaldehyde (238 mg, 1.64 mmol, 1.36 equiv) [Moyer, Mikel P.; Shiurba, John F.; Rapoport, Henry; J. Org. Chem.; 1986, 51, 5106-5110] was added to the solution of the 2-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-ylsulfanyl]-N-piperidin-3-ylmethyl-acetamide 1h (TFA)n (1.20 mmol, obtained from step 6) and diisopropylethylamine (0.85 mL, 4.8 mmol, 4 equiv) in 50 mL dichloroethane. Sodium triacetoxyborohydride (0.47 g, 2.24 mmol, 1.8 equiv) was added to the solution and the resulting suspension was stirred vigorously overnight. Methanol (5 mL) was added to quench the reaction. The mixture was concentrated and the residue was diluted with ethyl acetate. The solution was poured into saturated NaHCO3 solution (40 mL) and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), and concentrated. Chromatography on silica gel (10% methanol in chloroform) afforded 2-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-ylsulfanyl]-N-[1-(1H-indol-6-ylmethyl)-piperidin-3-ylmethyl]-acetamide (free base, 410 mg, 64%) as a light tan solid.

Workup

  1. customto quench
  2. customthe reaction
  3. concentrationThe mixture was concentrated
  4. additionthe residue was diluted with ethyl acetate
  5. additionThe solution was poured into saturated NaHCO3 solution (40 mL)
  6. extractionextracted with EtOAc
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-8f6715a2eeea41b2a1fc18a697f1497d
Source dataset
uspto-grants-2006_01
Patent number
US06984643B2

Reaction notes

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