Trimethylaluminum → HCID 68704545, compound

HRID 2261915Notes

Reaction equation

HRID 2261915 reaction equation
[C:1]([S:5](/[N:7]=[C:8](/[C:10]1[N:11]=[N:12][N:13]([C:15]2[CH:16]=[C:17]([CH:30]=[C:31]([N:33]([S:37]([CH3:40])(=[O:39])=[O:38])[CH2:34][CH2:35][CH3:36])[CH:32]=2)[C:18]([NH:20][C@@H:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:22])=[O:19])[CH:14]=1)\[CH3:9])=[O:6])([CH3:4])([CH3:3])[CH3:2].C[Al](C)C.[CH2:45]([Li])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C1(C)C=CC=CC=1>[C:1]([S:5]([NH:7][C:8]([C:10]1[N:11]=[N:12][N:13]([C:15]2[CH:16]=[C:17]([CH:30]=[C:31]([N:33]([S:37]([CH3:40])(=[O:38])=[O:39])[CH2:34][CH2:35][CH3:36])[CH:32]=2)[C:18]([NH:20][C@@H:21]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:22])=[O:19])[CH:14]=1)([CH3:9])[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:6])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 178456786HCID 178456786, compoundHCID 178506850HCID 178506850, compound2×

Product 1

HCID 68704545HCID 68704545, compoundYield 23.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 0° C. suspension of 0.03 g (0.05 mmol) 3-{4-[(1E)-N-(tert-butylsulfinyl)ethanimidoyl]-1H-1,2,3-triazol-1-yl}-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide in 5 mL toluene was added 0.1 mL (0.2 mmol, 2M solution in toluene) trimethylaluminum followed by 1 mL (approx. 0.2 mmol, 0.2 mM solution in ether) benzyllithium. The reaction mixture was stirred for 1 hr, then 0.4 mL more benzyllithium was added and the reaction mixture stirred for another hour at 0° C. The reaction was quenched by addition of 1 mL of saturated sodium sulfate solution and 50 mL EtOAc and stirred vigorously. To this was added MgSO4 and the resulting mixture was filtered through celite and concentrated. Purification by flash chromatography (1×8 cm silica gel, linear gradient 30-100% EtOAc/hexanes) afforded 8 mg 3-(4-{1-[(tert-butylsulfinyl)amino]-1-methyl-2-phenylethyl}-1H-1,2,3-triazol-1-yl)-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide which was dissolved in 1 mL methanol. To this was added 0.7 mL 2M HCl in ether. After 30 minutes the mixture was concentrated and purified by preparative HPLC (5->95% CH3CN/H2O over 30 min, 0.1% added TFA, C18 PRO YMC 20×150 mm) to afford 3 mg 3-[4-(1-amino-1-methyl-2-phenylethyl)-1H-1,2,3-triazol-1-yl]-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[(methylsulfonyl)(propyl)amino]benzamide as its trifluoroacetate salt. 1H NMR (CD3OD, 500 MHz) δ 8.55 (s, 1H), 8.28 (s, 1H), 8.04 (s, 1H), 7.99 (m, 1H), 7.42 (m, 2H), 7.26 (m, 3H), 7.07 (m, 2H), 7.00 (m, 2H), 5.25 (m, 1H), 3.77 (t, J=6.83 Hz, 2H), 3.47 (d, J=13 Hz, 1H), 3.27 (d, J=13 Hz, 1H), 3.01 (s, 3H), 1.76 (s, 3H), 1.59 (d, J=7.18 Hz, 3H), 1.53 (m, 2H), 0.95 (t, J=7.33 Hz, 3H). High resolution mass spec (FT/ICR) calc M+H=579.2548 found 578.2560.

Workup

  1. stirringthe reaction mixture stirred for another hour at 0° C
  2. customThe reaction was quenched by addition of 1 mL of saturated sodium sulfate solution and 50 mL EtOAc
  3. stirringstirred vigorously
  4. additionTo this was added MgSO4
  5. filtrationthe resulting mixture was filtered through celite and
  6. concentrationconcentrated
  7. customPurification by flash chromatography (1×8 cm silica gel, linear gradient 30-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-eef06d43021542fe81bd6f1225ca2403
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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