(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-(8-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-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate

HRID 501945Notes

Reaction equation

HRID 501945 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[N:8]([CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C@H:22]([CH2:37][C:38]3[CH:46]=[C:45]([CH3:47])[C:44]4[C:40](=[CH:41][N:42](COCC[Si](C)(C)C)[N:43]=4)[CH:39]=3)[C:23](=[O:36])[N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)[CH2:26][CH2:25]3)=[O:20])[CH2:15][CH2:14]1)[CH2:7]2>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[N:8]([CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C@H:22]([CH2:37][C:38]3[CH:39]=[C:40]4[C:44](=[C:45]([CH3:47])[CH:46]=3)[NH:43][N:42]=[CH:41]4)[C:23](=[O:36])[N:24]3[CH2:29][CH2:28][CH:27]([N:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)[CH2:26][CH2:25]3)=[O:20])[CH2:15][CH2:14]1)[CH2:7]2

Participants

3

Reactant 1

HCID 59424331(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-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate

Product 1

HCID 11599913(R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl 4-(8-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-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate (78 mg, 0.10 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 methanol/dichloromethane/triethylamine). The residue was dissolved in 10% methanol/dichloromethane and passed through a plug of basic alumina to give 40.1 mg (62%) as a white solid. 1H-NMR (CD3OD, 500 MHz) δ −0.20-0.30 (m, 0.6H), 0.80-1.20 (m, 0.7H), 1.40-2.35 (m, 16H), 2.45-2.83 (m, 6H), 2.90-3.48 (m, 5H), 4.00-4.83 (m, 7H), 5.71 (m, 0.3H), 5.79 (dd, J=9.5, 6.1, 0.7H), 7.00-7.25 (m, 3H), 7.25-7.41 (m, 1H), 7.69 (bs, 1H), 8.22 (bs, 1H). Mass spec.: 646.50 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (5:95:1 methanol/dichloromethane/triethylamine)
  3. dissolutionThe residue was dissolved in 10% methanol/dichloromethane
  4. customto give 40.1 mg (62%) as a white solid

Sources & evidence

ORD record
ord-53b94949703a45ef9701465f8c3a11a4
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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