Acetic Acid → HCID 70182119, compound

HRID 651343Notes

Reaction equation

HRID 651343 reaction equation
C(NCC(O)=O)(OC[CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=CC=[CH:9][CH:10]=2)=O.C1(CN2CC[C:37]3(N(C4C=CC=CC=4)C[N:39]([CH2:48][C:49]([OH:51])=[O:50])[C:38]3=[O:52])CC2)C2C(=CC=CC=2)C=CC=1.[CH:55]([N:58]=C=NC(C)C)(C)C.O[N:65]1[C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][C:68]=2N=N1.C([N:77]([CH:80]([CH3:82])C)[CH2:78][CH3:79])(C)C.[CH3:83][O-].[Na+].[C:86]([OH:89])(=O)[CH3:87]>CN(C)C=O.O1CCCC1.CO>[CH3:83][O:51][C:49](=[O:50])[CH2:48][N:39]([N:58]1[C:86](=[O:89])[C:87]2([CH2:79][CH2:78][N:77]([CH2:6][C:11]3[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH:5]=[CH:9][CH:10]=3)[CH2:80][CH2:82]2)[N:65]([C:69]2[CH:68]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH2:55]1)[C:38](=[O:52])[CH3:37]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 93124Fmoc-Gly-OHHCID 9932381HCID 9932381, compoundHCID 10942334Sodium Methoxide

Product 1

HCID 70182119HCID 70182119, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21899815MeOH tetrahydrofuranSolvent2×

Procedure

Wang resin loaded with Fmoc-glycine (88 mg, 0.045 mmol) was placed in a Teflon tube equipped with a frit on a mechanical shaker. The resin was allowed to swell in dimethyl formamide (1.5 ml) for 1 h. The solvent was removed by suction and the resin was agitated with 20% piperidine in N,N-dimethylformamide (1.5 ml) for 30 minutes. The solution was removed by suction and the resin was washed with N,N-dimethylformamide (3×1.5 ml). To a solution of (8-naphthalen-1-ylmethyl-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl)-acetic acid (0.0773 g, 0.18 mmol) in dimethyl formamide (1.6 ml), diisopropylcarbodiimide (29 μl, 0.18 mmol) and 1-hydroxy-1H-benzotriazol (0.0243 g, 0.18 mmol) were added and the mixture was stirred at room temperature for 0.5 h. The resulting solution and diisopropylethylamine (31 μl, 0.18 mmol) were added to the above resin and this was shaken at room temperature ovemight. The resin was filtered and washed with dimethylformamide (2×1.5 ml), dichloromethane (4×1.5 ml), methanol (2×1.5 ml) and tetrahydrofuran/methanol 4:1 (2×1.5 ml). A solution of sodium methoxide (0.009 mmol) in a mixture of tetrahydrofuran/methanol 4:1 (2 ml) was added to the resin and the suspension was agitated at 50 ° C. for 16 h. The mixture was neutralized by addition of a solution of acetic acid (0.01 mmol) in a mixture of tetrahydrofuran/methanol 4:1 (1 ml), the solution was drained and the resin was washed with tetrahydrofuran (1 ml). The combined filtrates were concentrated in vacuo to afford the title compound.

Workup

  1. customwas placed in a Teflon tube
  2. customequipped with a frit on a mechanical shaker
  3. customThe solvent was removed by suction
  4. customThe solution was removed by suction
  5. washthe resin was washed with N,N-dimethylformamide (3×1.5 ml)
  6. stirringthe mixture was stirred at room temperature for 0.5 h
  7. stirringthis was shaken at room temperature ovemight
  8. filtrationThe resin was filtered
  9. washwashed with dimethylformamide (2×1.5 ml), dichloromethane (4×1.5 ml), methanol (2×1.5 ml) and tetrahydrofuran/methanol 4:1 (2×1.5 ml)
  10. additionwas added to the resin
  11. stirringthe suspension was agitated at 50 ° C. for 16 h
  12. washthe resin was washed with tetrahydrofuran (1 ml)
  13. concentrationThe combined filtrates were concentrated in vacuo

Sources & evidence

ORD record
ord-a3d4177a52a24e28bd23ff372f74b0e8
Source dataset
uspto-grants-2001_08
Patent number
US06277991B1

Reaction notes

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