Trifluoroacetic acid → N,2-dimethylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 74762Notes

Reaction equation

HRID 74762 reaction equation
C(O[C:6]([N:8](C)[C:9]([CH3:59])([C:11]([NH:13][C@H:14]([C:18]([N:20]([C@@H:22]([C@@H:55]([CH3:58])[CH2:56][CH3:57])[C@H:23]([O:53][CH3:54])[CH2:24][C:25]([N:27]1[CH2:31][CH2:30][CH2:29][C@H:28]1[C@H:32]([O:51][CH3:52])[C@@H:33]([CH3:50])[C:34](=[O:49])[NH:35][C@H:36]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:26])[CH3:21])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH3:10])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:6][NH:8][C:9]([CH3:59])([C:11]([NH:13][C@H:14]([C:18]([N:20]([C@@H:22]([C@@H:55]([CH3:58])[CH2:56][CH3:57])[C@H:23]([O:53][CH3:54])[CH2:24][C:25]([N:27]1[CH2:31][CH2:30][CH2:29][C@H:28]1[C@H:32]([O:51][CH3:52])[C@@H:33]([CH3:50])[C:34](=[O:49])[NH:35][C@H:36]([C:44]1[S:45][CH:46]=[CH:47][N:48]=1)[CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:26])[CH3:21])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH3:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86685737N-(tert-butoxycarbonyl)-N,2-dimethylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 86685738N,2-dimethylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of #87 (58 mg, 0.068 mmol, 1 eq.) in dichloromethane (8 mL) was added trifluoroacetic acid (2 mL). After stirring overnight, the reaction mixture was concentrated in vacuo. The residue was taken up in ethyl acetate (10 mL), washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated in vacuo to give #88 (52 mg, quantitative). LC-MS 757.6 [M+H+], retention time=0.69 minute; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.64 (br d, J=8.6 Hz) and 8.87 (br d, J=8.6 Hz), total 1H], 7.80-7.85 (m, 1H), [7.77 (d, J=3.3 Hz) and 7.80 (d, J=3.1 Hz), total 1H], [7.63 (d, J=3.1 Hz) and 7.66 (d, J=3.3 Hz), total 1H], 7.20-7.31 (m, 4H), 7.13-7.19 (m, 1H), [5.39 (ddd, J=11, 8.5, 4 Hz) and 5.49-5.56 (m), total 1H], [4.51 (dd, J=9, 8 Hz) and 4.61 (dd, J=9, 8 Hz), total 1H], 3.16, 3.20, 3.21 and 3.25 (4 s, total 6H), 2.94 and 3.03 (2 br s, total 3H), 2.10 and 2.10 (2 s, total 3H), 1.16 (br s, 3H), 1.04-1.12 (m, 6H), 0.72-0.80 (m, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. washwashed with saturated aqueous sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give #88 (52 mg, quantitative)
  7. additiona mixture of rotamers, characteristic signals

Sources & evidence

ORD record
ord-39dfaf4a82f746af99c2c16422c88c6e
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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