Cyanuric chloride → HCID 57546116, compound

HRID 913930Notes

Reaction equation

HRID 913930 reaction equation
[NH2:1][C:2](=O)[CH:3]([C:26]1[C:34]2[C:30](=[CH:31][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:33]=2)[CH:29]=[C:28]([Cl:43])[CH:27]=1)[O:4][CH2:5][C:6]1([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.N1C(Cl)=NC(Cl)=NC=1Cl>CN(C)C=O>[Cl:43][C:28]1[CH:27]=[C:26]([CH:3]([C:2]#[N:1])[O:4][CH2:5][C:6]2([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[C:34]2[C:30](=[CH:31][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:33]=2)[CH:29]=1

Participants

4

Reactant 2

HCID 7954Cyanuric chlorideHCID 57546167tert-butyl 4-((2-amino-1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57546116HCID 57546116, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-((2-amino-1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (64 mg, 0.099 mmol) in dimethylformamide (0.7 mL) at 0° C. was added cyanuric chloride (18.2 mg, 0.10 mmol). The ice bath was removed and stirring continued for 5 h. The reaction was diluted with diethyl ether and quenched by addition of water. After stirring for 10 min, the ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (18%→25% ethyl acetate/n-hexane) gave 31 mg (50%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ0 8.08 (s, 1H), 7.68 (d, J=1.2 Hz, 1H), 7.29 (dd, J=8.6, 5.2 Hz, 2H), 7.24 (s, 1H), 7.00 (dd, J=8.9, 8.5 Hz, 2H), 5.71 (s, 1H), 5.69 (d, J=10.7 Hz, 1H), 5.64 (d, J=10.7 Hz, 1H), 3.76 (m, 3H), 3.61 (t, J=8.2 Hz, 2H), 3.58 (d, J=8.9 Hz, 1H), 3.03 (m, 2H), 2.14 (m, 2H), 1.90 (m, 2H), 1.43 (s, 9H), 0.92 (m, 2H), −0.03 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.0, 144.3, 137.6, 128.9 (d, J=8.6 Hz), 127.6, 125.9, 124.4, 122.92, 122.87, 121.0, 116.6, 115.4(d, J=21 Hz), 82.1, 79.6, 78.6, 68.0, 66.5, 41.2, 40.0 (br), 32.0, 28.5, 17.9, −1.3. Mass spec.: 629.35 (MH)+

Workup

  1. customThe ice bath was removed
  2. additionThe reaction was diluted with diethyl ether
  3. customquenched by addition of water
  4. stirringAfter stirring for 10 min
  5. washthe ethereal was washed with water (2×)
  6. dry with materialbrine, dried over magnesium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography (18%→25% ethyl acetate/n-hexane) gave 31 mg (50%) as a colorless oil

Sources & evidence

ORD record
ord-2c2403a54aa64406915db81fee39111c
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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