Trifluoroacetic acid → HCID 70675840, compound

HRID 403357Notes

Reaction equation

HRID 403357 reaction equation
FC(F)(F)C(O)=O.[O:8]=[C:9]1[NH:17][C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[N:10]1[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C@H:27]2[C:33]3[N:34]=[CH:35][S:36][C:32]=3[C@@H:31]([NH:37]C(OC(C)(C)C)=O)[C@H:30]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:46]=3[F:52])[CH2:29][CH2:28]2)=[O:25])[CH2:20][CH2:19]1>C(Cl)Cl>[O:8]=[C:9]1[NH:17][C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[N:10]1[CH:18]1[CH2:19][CH2:20][N:21]([C:24]([O:26][C@H:27]2[C:33]3[N:34]=[CH:35][S:36][C:32]=3[C@@H:31]([NH2:37])[C@H:30]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:46]=3[F:52])[CH2:29][CH2:28]2)=[O:25])[CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 70984732HCID 70984732, compound

Product 1

HCID 70675840HCID 70675840, compoundYield 92.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of trifluoroacetic acid (0.986 mL, 12.80 mmol) and (4R,7S,8S)-8-(tert-butoxycarbonylamino)-7-(2,3-difluorophenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[d]thiazol-4-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (16.4 mg, 0.026 mmol) in methylene chloride (10 mL) was stirred at rt from for 2.5 h. The solvent was removed under vacuum and the crude product was taken up in ethyl acetate and washed with saturated sodium bicarbonate. The ethyl acetate layer was separated, dried (sodium sulfate), filtered and concentrated. Flash chromatography, eluting with methanol in methylene chloride from 0 to 10% gave the desired product (13 mg, 89%) as a white solid: LCMS (M+H=541.40); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.98 (1H, br. s), 8.64 (1H, s), 8.08 (1H, d, J=4.8 Hz), 7.31-7.64 (1H, m), 6.94-7.19 (4H, m), 6.11-6.21 (1H, m), 4.42 (4H, m), 3.23-3.43 (1H, m), 2.85-3.16 (2H, m), 2.24 (6H, m), 1.83-1.98 (2H, m), 1.56 (2H, br.

Workup

  1. customThe solvent was removed under vacuum
  2. washwashed with saturated sodium bicarbonate
  3. customThe ethyl acetate layer was separated
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washFlash chromatography, eluting with methanol in methylene chloride from 0 to 10%

Sources & evidence

ORD record
ord-b92b2346ca1b4d1dab68242dd4d36aa8
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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