Triethylamine → 3-[1-[4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-ylbutanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-one

HRID 2099739Notes

Reaction equation

HRID 2099739 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:13][C:14](O)=[O:15])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.N1([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[NH:32][C:31](=[O:39])[N:30]=2)CCCCC1.C(N(CC)CC)C.CCOP(ON1N=[N:65][C:60]2C=[CH:62][CH:63]=[CH:64][C:59]=2C1=O)(OCC)=O>C(Cl)Cl.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][CH:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:13][C:14]([N:65]2[CH2:62][CH2:63][CH:64]([N:30]3[CH2:29][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[NH:32][C:31]3=[O:39])[CH2:59][CH2:60]2)=[O:15])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 160374384-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acidHCID 541506284-piperidinyl-2(1H)-quinazolinone

Product 1

HCID 114321833-[1-[4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-ylbutanoyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-oneYield 62%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(7-methyl-1H-indazol-5-yl)-3-pyridin-2-yl-butyric acid (white solid, 0.028 mmol) in methylene chloride (2 mL) was added 3,4-dihydro-3-(4-piperidinyl-2(1H)-quinazolinone (7.2 mg, 0.031 mmol, 1.1 equiv). Triethylamine (30 μL) was added followed by 3-(diethoxyphosphoryloxy)-1,2,3-benzotriain-4(3H)-one (DEPBT, 9.4 mg, 0.031 mmol 1.1 equiv). The resulting yellow solution was stirred at room temperature for 1 h and LCMS. A further 1 equivalent of the amine and DEPBT were added. After stirring for another 4 h, LCMS indicated complete conversion. The reaction mixture was diluted with ethyl acetate and quenched with 0.5 N sodium hydroxide. 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 (9.0 mg, 62% for two steps) as a glassy solid. MS (ESI) [M+H]+=509, 1H-NMR (400 MHz, CDCl3) δ 11.5 (br., 1H), 8.61-8.52 (m, 1H), 7.93 (d, J=4.8 Hz, 1H), 7.50-7.38 (m, 1H), 6.90 (m, 8H), 6.66 (d, J=7.6 Hz, 1H), 4.72-4.62 (m, 1H), 4.59-4.48 (m, 1H), 4.24 (s, 1H), 4.09 (s, 1H), 4.07-3.94 (m, 1H), 3.80-3.66 (m, 1H), 3.20-2.80 (m, 4H), 2.72-2.46 (m, 2H), 2.45 (d, J=4.8 Hz, 3H), 1.85-1.48 (m, 4H).

Workup

  1. stirringAfter stirring for another 4 h
  2. customquenched with 0.5 N sodium hydroxide
  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-09d626fee53a4427b30b8381985f713b
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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