Cesium fluoride → HCID 24863333, compound

HRID 2355856Notes

Reaction equation

HRID 2355856 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:54])[C@H:14]([NH:34][C:35]([N:37]3[CH2:42][CH2:41][CH:40]([N:43]4[CH2:52][C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[NH:45][C:44]4=[O:53])[CH2:39][CH2:38]3)=[O:36])[CH2:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21](S(CC[Si](C)(C)C)(=O)=O)[N:20]=[CH:19]4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+]>C(#N)C>[N:1]1([CH:7]2[CH2:8][CH2:9][N:10]([C:13](=[O:54])[C@H:14]([NH:34][C:35]([N:37]3[CH2:38][CH2:39][CH:40]([N:43]4[CH2:52][C:51]5[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=5)[NH:45][C:44]4=[O:53])[CH2:41][CH2:42]3)=[O:36])[CH2:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][N:20]=[CH:19]4)[CH2:11][CH2:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 25953Cesium fluorideHCID 58864471HCID 58864471, compound

Product 1

HCID 24863333HCID 24863333, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (R)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid {2-[1,4′]bipiperidinyl-1′-yl-2-oxo-1-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-ylmethyl]-ethyl}-amide (568 mg, 0.73 mmol) and cesium fluoride (1.11 g, 7.31 mmol) was heated at 80° C. in acetonitrile (50 mL) for 4.5 h. The reaction mixture was concentrated and the residue was subjected to flash column chromatography (methylene chloride/methanol/triethylamine, 94:5:1) to give 280 mg (63% yield) of the title compound as a white solid with 98.2% ee as determined by HPLC analysis using a Chirocel OD column with 20% B (A=ethanol, B=0.05% diethylamine in hexanes) as eluent (Retention times: 9.51 min for title compound and 15.9 min for S-enantiomer). 1H-NMR (CD3OD, 500 MHz) δ 8.04 (s, 0.75H), 8.03 (s, 0.25H), 7.67 (s, 0.75H), 7.65 (s, 0.25H), 7.56 (d, J=8.5 Hz, 0.75H), 7.51 (d, J=8.5 Hz, 0.25H), 7.41 (d, J=8.5 Hz, 0.75H), 7.31 (d, J=8.5 Hz, 0.25H), 7.19-7.12 (m, 2H), 6.97-6.94 (m, 1H), 6.80 (d, J=7.9 Hz, 1H), 5.08-5.05 (m, 1H), 4.60-4.53 (m, 1H), 4.48-4.40 (m, 1H), 4.37 (s, 1.5H), 4.26 (s, 0.5H), 4.24-4.14 (m, 2H), 4.06-3.97 (m, 1H), 3.15 (d, J=7.9 Hz, 1.5H), 3.12-3.05 (m, 0.5H), 2.94-2.86 (m, 3H), 2.57-2.51 (m, 1.5H), 2.47-2.42 (m, 1H), 2.37-2.33 (m, 0.75H), 2.03-2.02 (m, 1.5H), 1.87-1.75 (m, 3.75H), 1.73-1.68 (m, 2H), 1.67-1.54 (m, 3H), 1.53-1.44 (m, 4H), 1.43-1.34 (m, 2H), 1.30-1.26 (m, 1H), 0.83-0.77 (m, 0.75H), −0.16 to −0.24 (m, 0.75H). Mass spec.: 613 (MH)+.

Workup

  1. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-850e696aebe64ed9a2c2405805369bca
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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