Triethylamine → (+/-)-3-(1-(3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one

HRID 2099756Notes

Reaction equation

HRID 2099756 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:14][C:15]2[CH:23]=[C:22]([CH3:24])[C:21]3[C:17](=[CH:18][N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=3)[CH:16]=2)[CH2:10][C:11]([OH:13])=O)[CH:4]=1)[CH3:2].N1([C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[NH:42][C:41](=[O:49])[N:40]=2)CCCCC1.C(N(CC)CC)C.CCOP(ON1N=[N:75][C:70]2C=[CH:72][CH:73]=[CH:74][C:69]=2C1=O)(OCC)=O>C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]([CH2:14][C:15]2[CH:23]=[C:22]([CH3:24])[C:21]3[C:17](=[CH:18][N:19]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:20]=3)[CH:16]=2)[CH2:10][C:11]([N:75]2[CH2:72][CH2:73][CH:74]([N:40]3[CH2:39][C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[NH:42][C:41]3=[O:49])[CH2:69][CH2:70]2)=[O:13])[CH:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 541506284-piperidinyl-2(1H)-quinazolinoneHCID 57794674(+/-)-3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoic Acid

Product 1

HCID 57794597(+/-)-3-(1-(3-(4-Ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoyl)piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneYield 65%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (±)-3-(4-ethylpyridin-2-yl)-4-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)butanoic acid (0.166 mmol, 1.0 equiv) in methylene chloride (3 mL) was added 3,4-dihydro-3-(4-piperidinyl-2(1H)-quinazolinone (46 mg, 0.199 mmol, 1.2 equiv). Triethylamine (70 μL) was then added followed by 3-(diethoxyphosphoryloxy)-1,2,3-benzotriain-4(3H)-one (DEPBT, 60 mg, 0.199 mmol 1.2 equiv) under nitrogen. The resulted cloudy yellow solution was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and quenched with 0.5 N sodium hydroxide solution. The layers were separated and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (10% methanol in methylene chloride) to afford the desired product (72 mg, 65% for two steps): (ESI) 667 (MH)+.

Workup

  1. customThe resulted cloudy yellow solution
  2. customquenched with 0.5 N sodium hydroxide solution
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-07fc1620c5734c43b0dad20717179d64
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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