Trifluoroacetic anhydride → HCID 68311038, compound

HRID 529588Notes

Reaction equation

HRID 529588 reaction equation
C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.[NH2:14][C:15](=O)[CH2:16][C@H:17]([C:47](=[O:65])[NH:48][C@H:49]1[CH2:55][CH2:54][S:53][C@H:52]2[CH2:56][CH2:57][CH2:58][C@@H:59]([C:60]([O:62][CH3:63])=[O:61])[N:51]2[C:50]1=[O:64])[CH2:18][CH2:19][C@H:20]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:21]([NH:23][C@H:24]1[CH2:30][CH2:29][S:28][C@H:27]2[CH2:31][CH2:32][CH2:33][C@@H:34]([C:35]([O:37][CH3:38])=[O:36])[N:26]2[C:25]1=[O:39])=[O:22]>C(Cl)Cl>[CH2:40]([C@@H:20]([CH2:19][CH2:18][C@H:17]([CH2:16][C:15]#[N:14])[C:47]([NH:48][C@H:49]1[CH2:55][CH2:54][S:53][C@H:52]2[CH2:56][CH2:57][CH2:58][C@@H:59]([C:60]([O:62][CH3:63])=[O:61])[N:51]2[C:50]1=[O:64])=[O:65])[C:21]([NH:23][C@H:24]1[CH2:30][CH2:29][S:28][C@H:27]2[CH2:31][CH2:32][CH2:33][C@@H:34]([C:35]([O:37][CH3:38])=[O:36])[N:26]2[C:25]1=[O:39])=[O:22])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 68311207HCID 68311207, compound

Product 1

HCID 68311038HCID 68311038, compoundYield 52.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFAA (15 mg, 0.069 mmol) was slowly added to a 0° C. solution of Example 29 (27 mg, 0.034 mmol) and TEA (12.2 mg, 0.121 mmol) in DCM (0.25 mL). The reaction mixture was then stirred at rt for 1.5 hr. The reaction mixture was concentrated and the residue was partitioned between EtOAc and 10% aqueous Na2CO3. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified by RP prep-HPLC (Method A) to give dimethyl (4S,7S,10aS,4′S,7′S,10a′S)-4,4′-(((2R,5R)-2-benzyl-5-(cyanomethyl)-1,6-dioxo-1,6-hexanediyl)diimino)bis(5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate) (13 mg, 0.018 mmol, 51% yield). Anal. Calcd. for C37H49N5O8S2 m/z 755.7. found: 756.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (1H, d, J=6.6 Hz), 7.30-7.21 (3H, m), 7.20-7.11 (3H, m), 5.44-5.35 (2H, m), 5.18-5.00 (4H, m), 3.72 (3H, s), 3.69 (3H, s), 3.20 (1H, ddd, J=14.0, 10.7, 2.7 Hz), 3.15-3.01 (3H, m), 2.96 (1H, ddd, J=14.4, 7.0, 2.7 Hz), 2.91-2.82 (2H, m), 2.71 (1H, dd, J=13.2, 6.6 Hz), 2.65-2.55 (2H, m), 2.53-2.35 (4H, m), 2.25 (1H, ddd, J=10.7, 6.9, 3.3 Hz), 2.09-1.96 (4H, m), 1.82 (1H, td, J=7.1, 3.8 Hz), 1.78-1.51 (10H, m).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between EtOAc and 10% aqueous Na2CO3
  3. customThe organic phase was isolated
  4. washwashed with saturated aqueous NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by RP prep-HPLC (Method A)

Sources & evidence

ORD record
ord-c8f6821f17de443b85eafd6915127415
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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