Diisopropylethylamine → (R)-3-(7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-(7-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate

HRID 501952Notes

Reaction equation

HRID 501952 reaction equation
[C:1](=O)([O:37]C1C=CC([N+]([O-])=O)=CC=1)[O:2][C@H:3]([CH2:18][C:19]1[CH:27]=[C:26]([CH3:28])[C:25]2[C:21](=[CH:22][N:23]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:24]=2)[CH:20]=1)[C:4](=[O:17])[N:5]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:7][CH2:6]1.[F:48][C:49]1[CH:58]=[C:57]2[C:52]([CH2:53][N:54]([CH:60]3[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]3)[C:55](=[O:59])[NH:56]2)=[CH:51][CH:50]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[F:48][C:49]1[CH:58]=[C:57]2[C:52]([CH2:53][N:54]([CH:60]3[CH2:65][CH2:64][N:63]([C:1]([O:2][C@H:3]([CH2:18][C:19]4[CH:27]=[C:26]([CH3:28])[C:25]5[C:21](=[CH:22][N:23]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:35])([CH3:34])[CH3:36])[N:24]=5)[CH:20]=4)[C:4](=[O:17])[N:5]4[CH2:10][CH2:9][CH:8]([N:11]5[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]5)[CH2:7][CH2:6]4)=[O:37])[CH2:62][CH2:61]3)[C:55](=[O:59])[NH:56]2)=[CH:51][CH:50]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 594242967-fluoro-3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-oneHCID 59424375(R)-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-nitrophenyl carbonate

Product 1

HCID 59424349(R)-3-(7-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-(7-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-3-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-nitrophenyl carbonate (150 mg, 0.23 mmol) and 7-fluoro-3-(piperidin-4-yl)-3,4-dihydroquinazolin-2(1H)-one (56.2 mg, 1.0 equiv) in dimethylformamide (1 mL) was added diisopropylethylamine (79 μL, 0.45 mmol) and the reaction stirred at room temperature overnight. The reaction was concentrated and purified by column chromatography (3:97:1 methanol/dichloromethane/triethylamine) to give 93 mg (53%) as a tan foam solid. Mass spec.: 776.48 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (3:97:1 methanol/dichloromethane/triethylamine)
  3. customto give 93 mg (53%) as a tan foam solid

Sources & evidence

ORD record
ord-75954f159a3e49a798b4195ae60656e0
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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