Chlorotrimethylsilane → HCID 59263901, compound

HRID 644980Notes

Reaction equation

HRID 644980 reaction equation
Cl[Si](C)(C)C.[CH:6]1([NH:13][CH2:14][CH2:15][N:16]([CH2:27][CH2:28][C:29]2[C:37]3[S:36][C:35](=[O:38])[NH:34][C:33]=3[C:32]([OH:39])=[CH:31][CH:30]=2)[C:17](=[O:26])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.C(N(CC)CC)C.Cl[C:48](=[O:70])[CH2:49][CH2:50][N:51]([CH2:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)[C:52](=[O:61])[O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>ClCCl.C(OCC)(=O)C>[CH2:19]([O:18][C:17]([N:16]([CH2:27][CH2:28][C:29]1[C:37]2[S:36][C:35](=[O:38])[NH:34][C:33]=2[C:32]([OH:39])=[CH:31][CH:30]=1)[CH2:15][CH2:14][N:13]([CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1)[C:48](=[O:70])[CH2:49][CH2:50][N:51]([CH2:62][CH2:63][C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1)[C:52](=[O:61])[O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 59263939HCID 59263939, compoundHCID 59263951HCID 59263951, compound

Product 1

HCID 59263901HCID 59263901, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Chlorotrimethylsilane (1.323 mL) was added to a cooled (0° C.) solution of benzyl 2-(cycloheptylamino)ethyl(2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)carbamate, prepared as in Example 23 step i) (1.260 g) and triethylamine (1.81 mL) in dichloromethane (35 mL). The reaction mixture was stirred at room temperature for 2 h then a solution of benzyl 3-chloro-3-oxopropyl(phenethyl)carbamate, prepared as in Example 5 step ii) (0.991 g) in dichloromethane (10 mL) was added. The reaction mixture was stirred at room temperature for 4 h then diluted with ethyl acetate and washed with 2M hydrochloric acid (×2) and saturated sodium hydrogen carbonate. The organic layer was separated, washed with water and saturated brine, dried over sodium sulphate, filtered and evaporated. The crude product was purified by flash silica chromatography (Biotage), elution gradient 1 to 6% methanol in dichloromethane. Fractions containing product were evaporated to dryness to afford the product as a yellow foam (1.416 g). The material was used in the next step directly.

Workup

  1. temperaturea cooled
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 4 h
  4. washwashed with 2M hydrochloric acid (×2) and saturated sodium hydrogen carbonate
  5. customThe organic layer was separated
  6. washwashed with water and saturated brine
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography (Biotage), elution gradient 1 to 6% methanol in dichloromethane
  11. additionFractions containing product
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-4f9287c592e6409e9ef95583f7ea6db2
Source dataset
uspto-grants-2010_04
Patent number
US07700782B2

Reaction notes

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