Trimethylsilyl triflate → HCID 67959500, compound

HRID 1895803Notes

Reaction equation

[CH2:1]([O:7][C:8]([C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:48])[C@@H:17]([NH:33][C:34](=[O:47])[C@@H:35]([NH:39][C:40](OC(C)(C)C)=[O:41])[CH:36]([CH3:38])[CH3:37])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH:20]=2)[NH:11]1)=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(N(CC)C(C)C)(C)C.[CH3:70][O:71][C@@H:72]([CH2:78][CH2:79][CH:80]=[CH2:81])[C@H:73](C)[C:74](O)=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl.CN(C)C=O.[Cl-].[Na+].O>[CH2:1]([O:7][C:8]([C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:48])[C@@H:17]([NH:33][C:34](=[O:47])[C@@H:35]([NH:39][C:40](=[O:41])[C@H:73]([CH3:74])[C@H:72]([O:71][CH3:70])[CH2:78][CH2:79][CH:80]=[CH2:81])[CH:36]([CH3:38])[CH3:37])[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH:20]=2)[NH:11]1)=[O:9])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethylsilanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid hex-5-enyl ester in anhydrous dichloromethane (12 mL) was cooled to 0° C. before adding trimethylsilyl trifluoromethanesulfonate (242 μL, 1.088 mmol). The reaction mixture was stirred at 0° C. under a nitrogen atmosphere for 3.5 hours, then N,N-diisopropylethylamine (480 μL, 2.903 mmol) was added. The reaction mixture was evaporated to give the crude amine as a colourless gum. A solution of (2S,3S)-3-methoxy-2-methyl-hept-6-enoic acid in anhydrous N,N-dimethylformamide (6 mL) was cooled to 0° C., before adding 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (276 mg, 0.726 mmol) and N,N-diisopropylethylamine (480 μL, 2.903 mmol). It was stirred at 0° C. for 20 minutes before adding a solution of the crude amine in N,N-dimethylformamide (10 mL). The reaction mixture was stirred at room temperature for 16 hours then diluted with brine (20 mL) and extracted with ethyl acetate (3×15 mL). The extract was further washed with brine (2×15 mL) then dried over anhydrous sodium sulfate and evaporated to give a brown oil. The oil was purified by silica gel chromatography using ethyl acetate/iso-hexanes 1:1, then ethyl acetate/iso-hexanes 7:3 to give the title compound (187 mg, 35%) as a white solid. 1H NMR (300 MHz, CDCl3) δ0.19 (s, 6H), 0.83-1.00 (m, 7H), 0.98 (s, 9H), 1.16 (d, J=7.1 Hz, 3H), 1.20-1.30 (m, 3H), 1.36-1.55 (m, 3H), 1.58-1.72 (m, 3H), 1.73-1.90 (m, 2H), 2.03-2.24 (m, 4H), 2.41-2.55 (m, 1H), 2.65-3.00 (m, 3H), 3.31-3.44 (m, 1H), 3.39 (s, 3H), 3.57 (d, J=11.4 Hz, 1H), 4.05-4.19 (m, 2H), 4.25-4.40 (m, 2H), 4.92-5.10 (m, 4H), 5.65-5.90 (m, 3H), 6.41-6.57 (m, 2H), 6.65 (s, 1H), 6.69 (d, J=8.0 Hz, 1H), 6.81 (d, J=6.9 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H). LCMS (m/z) 743.46 [M+H] Tr=5.97 min.

Workup

customThe reaction mixture was evaporated
customto give the crude amine as a colourless gum
stirringIt was stirred at 0° C. for 20 minutes
stirringThe reaction mixture was stirred at room temperature for 16 hours
extractionextracted with ethyl acetate (3×15 mL)
washThe extract was further washed with brine (2×15 mL)
dry with materialthen dried over anhydrous sodium sulfate
customevaporated
customto give a brown oil
customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record: ord-4e007a9aac184e65ad8f208342eba7b9
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513184B2

Reaction notes

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