Triacetoxyperiodinane → 4-(4-isopropylpiperazin-1-yl)-N-((S)-1-((3aS,6R,6aS)-6-methoxy-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)benzamide

HRID 1716469Notes

Reaction equation

HRID 1716469 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[OH:23][C@@H:24]1[C@H:28]2[N:29]([C:34](=[O:59])[C@@H:35]([NH:41][C:42](=[O:58])[C:43]3[CH:48]=[CH:47][C:46]([N:49]4[CH2:54][CH2:53][N:52]([CH:55]([CH3:57])[CH3:56])[CH2:51][CH2:50]4)=[CH:45][CH:44]=3)[CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:30][C@@H:31]([O:32][CH3:33])[C@H:27]2[O:26][CH2:25]1>ClCCl>[CH:55]([N:52]1[CH2:51][CH2:50][N:49]([C:46]2[CH:45]=[CH:44][C:43]([C:42]([NH:41][C@@H:35]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:34]([N:29]3[CH2:30][C@@H:31]([O:32][CH3:33])[C@H:27]4[O:26][CH2:25][C:24](=[O:23])[C@@H:28]34)=[O:59])=[O:58])=[CH:48][CH:47]=2)[CH2:54][CH2:53]1)([CH3:57])[CH3:56]

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 68510175N-((S)-1-((3R,3aR,6R,6aS)-3-hydroxy-6-methoxydihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)-4-(4-isopropylpiperazin-1yl)benzamide

Product 1

HCID 250068914-(4-isopropylpiperazin-1-yl)-N-((S)-1-((3aS,6R,6aS)-6-methoxy-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dess-Martin periodinane (2.82 g, 6.66 mmol) was added to a stirred solution of N—((S)-1-((3R,3aR,6R,6aS)-3-hydroxy-6-methoxydihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)-4-(4-isopropylpiperazin-1yl)benzamide (1.72 g, 3.33 mmol) in dichloromethane (65 mL) under an atmosphere of argon. The mixture was stirred for 18 hours then diluted with dichloromethane (300 mL). The organic phase was washed with aqueous sodium hydroxide solution (1M, 100 mL) then the aqueous extracted with dichloromethane (150 mL). The organic layer was washed with aqueous sodium hydroxide solution (1M, 100 mL) then brine (150 mL), then dried (Na2SO4), filtered and reduced in vacuo to give 4-(4-isopropylpiperazin-1-yl)-N—((S)-1-((3aS,6R,6aS)-6-methoxy-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)benzamide a pale yellow solid (1.408 g, 82%). TLC (Rf=0.45, MeOH:CH2Cl2 1:19), analytical HPLC main peak, Rt=10.39 min., HPLC-MS 515.3 [M+H]+, 533.3 [M+H2O+H]+, 1051.6 [2M+Na]+; [□]D22−31.08° (c=3.7, CHCl3); δH (500 MHz, CDCl3) 0.99 (9H, s, C(CH3)3), 1.08 (6H, d, J=6.52 Hz, NCH(CH3)2), 1.68-1.74 (2H, m, CH2C(CH3)3), 2.65 (4H, brt, J=5.04 Hz, CH2NCH(CH3)2), 2.67-2.73 (1H, m, NCH(CH3)2), 3.29 (4H, brt, J=5.05 Hz, CH2CH2NCH(CH3)2), 3.49 (3H, s, OCH3), 3.61 (1H, dd, 5.35 Hz, NCH2CHOCH3), 4.00-4.04 (1H, m, CHOCH3), 4.09 (1H, d, J=16.89 Hz, OCH2C═O), 4.20 (1H, d, J=16.93 Hz, OCH2C═O), 4.27 (1H, dd, 5.88 Hz, NCH2CHOCH3), 4.74 (1H, d, J=6.86 Hz, OCH2(C═O)CH), 4.91 (1H, dd, 4.28 Hz, OCHCHOCH3), 4.94-5.00 (1H, m, CHCH2C(CH3)3), 6.61 (1H, d, J=8.69 Hz, NH), 6.84 (2H, brd, J=8.95 Hz, aromatic CH), 7.65 (2H, brd, J=8.91 Hz, aromatic CH); δC (125 MHz, CDCl3) 18.53 (NCH(CH3)2), 29.75/29.80 (C(CH3)3), 30.75/30.77 (C(CH3)3), 46.53 (CH2C(CH3)3), 47.02 (NCH2CH2NCH(CH3)2), 48.24 (CHCH2C(CH3)3), 48.43 (NCH2CH2NCH(CH3)2), 49.76 (NCH2CHOCH3), 54.49 (NCH(CH3)2), 58.23 (OCH3), 60.49 (OCH2C(═O)CH), 71.45 (OCH2C═O), 78.84 (CHOCH3), 80.25 (OCHCHOCH3), 114.01/114.10/128.49 and 129.83 (aromatic CH), 123.08 (aromatic quaternary), 153.55 (aromatic quaternary), 166.69 (NHC═O), 173.53 (CH2NC═O), 207.93 (ketone C═O).

Workup

  1. washThe organic phase was washed with aqueous sodium hydroxide solution (1M, 100 mL)
  2. extractionthe aqueous extracted with dichloromethane (150 mL)
  3. washThe organic layer was washed with aqueous sodium hydroxide solution (1M, 100 mL)
  4. dry with materialbrine (150 mL), then dried (Na2SO4)
  5. filtrationfiltered

Sources & evidence

ORD record
ord-11804fe727b04256a41a1c298bac0a3c
Source dataset
uspto-grants-2010_09
Patent number
US07803803B2

Reaction notes

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