Trifluoroacetic acid → HCID 69316994, compound

HRID 1391717Notes

Reaction equation

HRID 1391717 reaction equation
C(O)(C(F)(F)F)=O.[CH2:8]([O:11][C@H:12]1[C:20]2[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=2)[C@@H:14]([NH:23][CH2:24][C@@H:25]([OH:49])[C@@H:26]([NH:36][C:37](=[O:48])[C@@H:38]([N:42]2[CH2:46][CH2:45][CH2:44][C:43]2=[O:47])[CH2:39][CH:40]=[CH2:41])[CH2:27][C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=2)[CH2:13]1)C=C>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[F:35][C:30]1[CH:29]=[C:28]([CH:33]=[C:32]([F:34])[CH:31]=1)[CH2:27][C@@H:26]1[NH:36][C:37](=[O:48])[C@@H:38]([N:42]2[CH2:46][CH2:45][CH2:44][C:43]2=[O:47])[CH2:39][CH:40]=[CH:41][CH2:8][O:11][C@@H:12]2[CH2:13][C@@H:14]([C:15]3[CH:16]=[C:17]([O:21][CH3:22])[CH:18]=[CH:19][C:20]=32)[NH:23][CH2:24][C@H:25]1[OH:49]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 58813120HCID 58813120, compound

Product 1

HCID 69316994HCID 69316994, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 178479819HCID 178479819, compoundCatalyst

Procedure

Step I (2): The TFA salt of (S)—N-((2S,3R)-4-((1S,3R)-3-(Allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)-2-(2-oxopyrrolidin-1-yl)pent-4-enamide (diastereomer A, 10 mg, 0.0143 mmol) from stepG(1) was dissolved in 2 mL of CH2CL2. Added Hoveyda/Grubbs catalyst [(1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(O-isoproproxylphenylmethylene)ruthenium] (2.4 mg, 2.9 μmol, Aldrich) and stirred at room temperature overnight. Evaporated to dryness. Dissolved in MeOH and filtered. The crude product was purified using reverse phase preparatory HPLC to give 5.5 mg (70% yield) of the title compound as its TFA salt: LC-MS (M+H)+=556.31; HRMS (M+H)+=556.2603; 1H NMR (500 MHz, CDCl3) δ 7.27-7.43 (m, 1H), 7.04-7.21 (m, 1H), 6.99 (d, J=8.24 Hz, 1H), 6.40-6.83 (m, 3H), 5.42-5.79 (m, 2H), 4.98 (d, J=5.49 Hz, 1H), 4.71 (d, J=5.49 Hz, 1H), 4.25-4.51 (m, 1H), 4.06 (d, J=8.24 Hz, 1H), 3.87-4.06 (m, 2H), 3.72-3.91 (m, 3H), 3.36-3.72 (m, 3H), 3.16-3.39 (m, 2H), 3.06-3.21 (m, 1H), 2.92-3.08 (m, 1H), 2.76-2.89 (m, 1H), 2.54-2.76 (m, 2H), 2.17-2.54 (m, 3H), 1.86 (dd, J=14.34, 7.32 Hz, 2H), 0.91-1.52 (m, 2H).

Workup

  1. customEvaporated to dryness
  2. dissolutionDissolved in MeOH
  3. filtrationfiltered
  4. customThe crude product was purified

Sources & evidence

ORD record
ord-a63bc8ab9ad942d2b0d2e78f3d89f1ec
Source dataset
uspto-grants-2008_03
Patent number
US07338974B2

Reaction notes

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