HCID 131735531, compound → HCID 117599042, compound

HRID 522388Notes

Reaction equation

HRID 522388 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[C:23]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N:17]=[C:16]2[O:24][C@H:25]3[CH2:51][N:28]([C:29](=[O:50])[C@H:30]([CH:45]4[CH2:49][CH2:48][CH2:47][CH2:46]4)[NH:31][C:32](=[O:44])[O:33][C@@H:34]4[CH2:43][CH2:42][CH2:41][C@H:35]4[CH2:36][CH2:37][CH:38]=[CH:39][CH2:40][C:15]=12)[C@H:27]([C:52]([NH:54][C@:55]1([C:60](=[O:68])[NH:61][S:62]([CH:65]2[CH2:67][CH2:66]2)(=[O:64])=[O:63])[CH2:57][C@H:56]1[CH:58]=[CH2:59])=[O:53])[CH2:26]3)(C(C)(C)C)(C)C>C1COCC1>[CH:45]1([C@H:30]2[C:29](=[O:50])[N:28]3[CH2:51][C@@H:25]([CH2:26][C@H:27]3[C:52]([NH:54][C@:55]3([C:60](=[O:68])[NH:61][S:62]([CH:65]4[CH2:66][CH2:67]4)(=[O:63])=[O:64])[CH2:57][C@H:56]3[CH:58]=[CH2:59])=[O:53])[O:24][C:16]3=[N:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=4[C:14]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][OH:8])=[C:15]3[CH2:40][CH:39]=[CH:38][CH2:37][CH2:36][C@@H:35]3[CH2:41][CH2:42][CH2:43][C@H:34]3[O:33][C:32](=[O:44])[NH:31]2)[CH2:49][CH2:48][CH2:47][CH2:46]1

Participants

3

Reactant 1

HCID 131735531HCID 131735531, compound

Product 1

HCID 117599042HCID 117599042, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the product of Step 1 (50 mg) in THF (0.5 mL) was added HF-TEA (0.334 mL) at room temperature. The solution was heated to 50° C. for 30 minutes. The reaction mixture was concentrated to remove THF and then diluted with EtOAc (10 mL) and water was added (10 mL). To that mixture was added Na2CO3 (353 mg) portion wise at 0° C. When the quench was complete, the layers were separated. The organic layer was washed with 10% Na2CO3, water and brine. The aqueous layer was re-extracted with ethyl acetate (2×). The combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (40-100% ACN/water with 0.15% TFA) afforded the desired product (7.2 mg) after workup with NaHCO3 and ethyl acetate. HRMS (ES+) m/z 862.4073 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove THF
  3. additiondiluted with EtOAc (10 mL) and water
  4. additionwas added (10 mL)
  5. additionTo that mixture was added Na2CO3 (353 mg) portion wise at 0° C
  6. customthe layers were separated
  7. washThe organic layer was washed with 10% Na2CO3, water and brine
  8. extractionThe aqueous layer was re-extracted with ethyl acetate (2×)
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by reverse phase HPLC (40-100% ACN/water with 0.15% TFA)

Sources & evidence

ORD record
ord-1bfa5e7874e94fe28d0dc25408df12ac
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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