Trifluoroacetic acid → HCID 89544598, compound

HRID 630672Notes

Reaction equation

HRID 630672 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:37][CH2:38][NH:39][C:40]([O:42][C:43]1[CH:48]=[CH:47][C:46]([CH2:49][C@H:50]([NH:60]C(OC(C)(C)C)=O)[C:51]([NH:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:52])=[CH:45][CH:44]=1)=[O:41])[C:9]([NH:11][C@@H:12]([CH2:16][S:17]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:13]([NH2:15])=[O:14])=[O:10])(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[CH2:83]([N:90]1[C:94](=[O:95])[CH:93]=[CH:92][C:91]1=[O:96])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1>ClC(Cl)C.O>[NH2:7][C@H:8]([C:9]([NH:11][C@@H:12]([CH2:16][S:17][CH:92]1[CH2:93][C:94](=[O:95])[N:90]([CH2:83][C:84]2[CH:85]=[CH:86][CH:87]=[CH:88][CH:89]=2)[C:91]1=[O:96])[C:13]([NH2:15])=[O:14])=[O:10])[CH2:37][CH2:38][NH:39][C:40]([O:42][C:43]1[CH:48]=[CH:47][C:46]([CH2:49][C@@H:50]([C:51]([NH:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:52])[NH2:60])=[CH:45][CH:44]=1)=[O:41]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 74204BenzylmaleimideHCID 126503884HCID 126503884, compound

Product 1

HCID 89544598HCID 89544598, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

238 mg (0.25 mmol) of the compound of example 1B was dissolved in 10 ml dichloroethane. 0.12 ml Triethylsilane, approx. 10 ml trifluoroacetic acid and approx. 0.5 ml water was added. The reaction mixture was stirred for approx. 30 min at room temperature. 100 ml dichloroethane were added and the reaction mixture was evaporated under reduced pressure to approx. 1 ml of solvent volume. Approx. 100 ml water was added and the reaction mixture was extracted three times with approx. 50 ml dichloromethane. To the aqueous phase 15 ml of acetic acid was added. The aqueous phase was frozen and lyophilized. The lyophylistae was dissolved in approx. 50 ml methanol and 0.183 mg (0.98 mmol) N-benzylmaleimide was added. The reaction mixture was stirred over night at room temperature. The reaction mixture was evaporated to dryness and redissolved in approx. 5 ml methanol and purified by preparative RP-HPLC on a C18 with a water/methanol gradient. The fractions were collected in test tubes of 20 ml on an automated fraction collector. To ensure sufficient acidity each vial was filled with 0.5 ml acedic acid prior to collection. All fractions containing the compound of example 1C were combined. Acetonitrile was partially removed on a rotary evaporator at 30° C. water bath temperature and approx. 50 mbar for approx. 30 min. After addition of 0.5 ml acedic acid, the remaining solution was lyophilized. The total yield was 168 mg (0.24 mmol, 98% of theory) of the desired product.

Workup

  1. customthe reaction mixture was evaporated under reduced pressure to approx. 1 ml of solvent volume
  2. additionApprox. 100 ml water was added
  3. extractionthe reaction mixture was extracted three times with approx. 50 ml dichloromethane
  4. additionTo the aqueous phase 15 ml of acetic acid was added
  5. temperatureThe aqueous phase was frozen
  6. dissolutionThe lyophylistae was dissolved in approx. 50 ml methanol
  7. stirringThe reaction mixture was stirred over night at room temperature
  8. customThe reaction mixture was evaporated to dryness
  9. dissolutionredissolved in approx. 5 ml methanol
  10. custompurified by preparative RP-HPLC on a C18 with a water/methanol gradient
  11. customThe fractions were collected in test tubes of 20 ml on an automated fraction collector
  12. additionwas filled with 0.5 ml acedic acid
  13. customto collection
  14. additionAll fractions containing the compound of example 1C
  15. customAcetonitrile was partially removed on a rotary evaporator at 30° C. water bath temperature and approx. 50 mbar for approx. 30 min
  16. additionAfter addition of 0.5 ml acedic acid

Sources & evidence

ORD record
ord-67859f4648634637b27a1693c0560a26
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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