Triethylamine → HCID 49787495, compound

HRID 244361Notes

Reaction equation

HRID 244361 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[S:14]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)(=[O:16])=[O:15].[CH:27]([N:30]=[C:31]=[O:32])([CH3:29])[CH3:28].C(N(CC)CC)C>C(Cl)Cl>[C:10]([C:9]1[CH:12]=[CH:13][C:6]([O:5][C:4]2[CH:3]=[C:2]([CH3:1])[CH:25]=[C:24]([CH3:26])[CH:23]=2)=[C:7]([S:14]([N:17]2[CH2:22][CH2:21][N:20]([C:31]([NH:30][CH:27]([CH3:29])[CH3:28])=[O:32])[CH2:19][CH2:18]2)(=[O:16])=[O:15])[CH:8]=1)#[N:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 61277Isopropyl isocyanateHCID 10133817HCID 10133817, compound

Product 1

HCID 49787495HCID 49787495, compoundYield 11.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of compound 24 (0.100 g, 0.27 mmol) in CH2Cl2 (3 mL) was added isopropyl isocyanate (0.032 g, 0.38 mmol) and triethylamine (0.039 g, 0.38 mmol). Reaction was stirred for 20 hrs at room temperature, whereupon the starting material was consumed (TLC, 1% MeOH in CH2Cl2). The reaction mixture was then concentrated in vacuo, redissolved in a minimal amount of CH2Cl2, and chromatographed over normal phase silica (MeOH/CH2Cl2). The fractions containing the desired product were combined and concentrated in vacuo to yield a white powder, which was then triturated with CH2Cl2/hexanes and vacuum filtered to yield a powder. The powder was redissolved in CH2Cl2 and chromatographed for a second time over normal phase silica (MeOH/CH2Cl2). The fractions containing the desired product were combined and concentrated in vacuo to yield a white powder, which was then triturated with hexanes and vacuum filtered to afford compound 58 as a white powder (0.014 g, 11.3% yield, 99.1% HPLC purity). 1H NMR (500 MHz, CDCl3): 8.27 (d, J=2 Hz, 1H), 7.67 (dd, J1=9 Hz, J2=2 Hz, 1H) 6.93 (s, 1H), 6.89 (s, J=9 Hz, 1H), 6.69 (s, 2H), 4.17 (m, 1H), 3.95 (m, 1H), 3.44 (m, 4H), 335 (m, 4H), 2.34 (s, 6H), 1.14 (d, J=7 Hz, 6H); MS (ESI, EE): m/z=457 (MH+).

Workup

  1. customReaction
  2. customwas consumed (TLC, 1% MeOH in CH2Cl2)
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. dissolutionredissolved in a minimal amount of CH2Cl2
  5. customchromatographed over normal phase silica (MeOH/CH2Cl2)
  6. additionThe fractions containing the desired product
  7. concentrationconcentrated in vacuo
  8. customto yield a white powder, which
  9. customwas then triturated with CH2Cl2/hexanes and vacuum
  10. filtrationfiltered
  11. customto yield a powder
  12. customchromatographed for a second time over normal phase silica (MeOH/CH2Cl2)
  13. additionThe fractions containing the desired product
  14. concentrationconcentrated in vacuo
  15. customto yield a white powder, which
  16. customwas then triturated with hexanes and vacuum
  17. filtrationfiltered

Sources & evidence

ORD record
ord-be244e6ae720416aa3b027b342c2aba8
Source dataset
uspto-grants-2014_02
Patent number
US08658642B2

Reaction notes

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