(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 → (R)-3-(7-Methyl-1H-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 501953Notes

Reaction equation

HRID 501953 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][N:7]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C@H:22]([CH2:37][C:38]4[CH:46]=[C:45]([CH3:47])[C:44]5[C:40](=[CH:41][N:42](COCC[Si](C)(C)C)[N:43]=5)[CH:39]=4)[C:23](=[O:36])[N:24]4[CH2:29][CH2:28][CH:27]([N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:26][CH2:25]4)=[O:20])[CH2:15][CH2:14]3)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][N:7]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C@H:22]([CH2:37][C:38]4[CH:39]=[C:40]5[C:44](=[C:45]([CH3:47])[CH:46]=4)[NH:43][N:42]=[CH:41]5)[C:23](=[O:36])[N:24]4[CH2:29][CH2:28][CH:27]([N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)[CH2:26][CH2:25]4)=[O:20])[CH2:15][CH2:14]3)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1

Participants

3

Reactant 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

Product 1

HCID 11549159(R)-3-(7-Methyl-1H-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 6422Trifluoroacetic acidSolvent

Procedure

(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 (93 mg, 0.12 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 6 mL) and stirred at room temperature for 2 h. The reaction was concentrated and purified by column chromatography (5:95:1 to 10:90:1 methanol/dichloromethane/triethylamine). The residue was dissolved in 10% methanol/dichloromethane and passed through a plug of basic alumina to give 41 mg (53%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ −0.38-0.15 (m, 0.7H), 0.60-0.95 (m, 1H), 1.18-2.18 (m, 17H), 2.29 (m, 0.7H), 2.35-2.50 (m, 3H), 2.58-3.01 (m, 3.4H), 3.01-3.25 (m, 2.4H), 3.65-4.60 (m, 7H), 5.47 (m, 0.4H), 5.55 (dd, J=9.5, 6.1, 0.7H), 6.51 (m, 0.8H), 6.62 (m, 0.8H), 6.90-7.20 (m, 2.2H), 7.45 (bs, 1.1H), 7.98 (bs, 1H). Mass spec.: 648.64 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (5:95:1 to 10:90:1 methanol/dichloromethane/triethylamine)
  3. dissolutionThe residue was dissolved in 10% methanol/dichloromethane
  4. customto give 41 mg (53%) as a white powder

Sources & evidence

ORD record
ord-2abe5c7a24824a22b487d506785537b7
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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