HCID 58813159, compound → (1S,4R,5S,8S,14R)-5-Benzyl-4-hydroxy-8-((S)-3-isobutyl-2-oxo-pyrrolidin-1-yl)-18-methoxy-13-oxa-2,6-diaza-tricyclo[12.6.1.015,20]henicosa-10,15(20),16,18-tetraen-7-one

HRID 1391722Notes

Reaction equation

HRID 1391722 reaction equation
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:44])[C@@H:19]([NH:27][C:28](=[O:43])[C@@H:29]([N:33]2[CH2:37][CH2:36][C@H:35]([CH2:38][CH:39]([CH3:41])[CH3:40])[C:34]2=[O:42])[CH2:30][CH:31]=[CH2:32])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6]1)C=C>C(Cl)Cl>[CH2:20]([C@@H:19]1[NH:27][C:28](=[O:43])[C@@H:29]([N:33]2[CH2:37][CH2:36][C@H:35]([CH2:38][CH:39]([CH3:40])[CH3:41])[C:34]2=[O:42])[CH2:30][CH:31]=[CH:32][CH2:1][O:4][C@@H:5]2[CH2:6][C@@H:7]([C:8]3[CH:9]=[C:10]([O:14][CH3:15])[CH:11]=[CH:12][C:13]=32)[NH:16][CH2:17][C@H:18]1[OH:44])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

3

Reactant 1

HCID 58813159HCID 58813159, compound

Product 1

HCID 86610863(1S,4R,5S,8S,14R)-5-Benzyl-4-hydroxy-8-((S)-3-isobutyl-2-oxo-pyrrolidin-1-yl)-18-methoxy-13-oxa-2,6-diaza-tricyclo[12.6.1.015,20]henicosa-10,15(20),16,18-tetraen-7-oneYield 87.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Hoveyda-Grubb's 2nd generation catalyst (3.01 mg, 3.55 μmol) was added to flask charge with a solution of (S)—N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-hydroxy-1-phenylbutan-2-yl)-2-((S)-3-isobutyl-2-oxopyrrolidin-1-yl)pent-4-enamide (25.5 mg, 35.5 μmol, TFA salt) from step 0 (1) in DCM (4 mL) at RT. The mixture was stirred for 16 h. Evaporated to dryness. Dissolved in MeOH and filtered. Purified with reverse phase Prep-HPLC to give 17.9 mg (75%) of the (1S,4R,5S,8S,14R)-5-Benzyl-4-hydroxy-8-((S)-3-isobutyl-2-oxo-pyrrolidin-1-yl)-18-methoxy-13-oxa-2,6-diaza-tricyclo[12.6.1.015,20]henicosa-10,15(20),16,18-tetraen-7-one as the TFA salt: LC-MS (M+H)+=576.2, HRMS (M+H)+=576.3447; 1H NMR (500 MHz, CDCl3) 8 ppm 0.91 (dd, J=32.81, 5.95 Hz, 4H) 1.11 (t, J=9.77 Hz, 1H) 1.30-1.44 (m, 1H) 1.55-1.72 (m, 2H) 2.03 (dd, J=13.12, 4.58 Hz, 2H) 2.28-2.76 (m, 12H) 3.14 (s, 3H) 3.72-3.92 (m, 3H) 4.04-4.19 (m, 2H) 4.40 (s, 1H) 4.72 (d, J=4.58 Hz, 1H) 4.83-4.96 (m, 1H) 5.51-5.74 (m, 1H) 6.92-7.30 (m, 8H) 7.35 (t, J=8.39 Hz, 1H).

Workup

  1. customEvaporated to dryness
  2. dissolutionDissolved in MeOH
  3. filtrationfiltered
  4. customPurified with reverse phase Prep-HPLC

Sources & evidence

ORD record
ord-5e0ddc8d491246ab8c583dee2f801a15
Source dataset
uspto-grants-2008_03
Patent number
US07338974B2

Reaction notes

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