HCID 86701796, compound → HCID 86701795, compound

HRID 338635Notes

Reaction equation

HRID 338635 reaction equation
[O:1]=[S:2]1(=[O:51])[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[CH2:9][C:10]([NH:12][C@:13]12[CH2:47][CH2:46][C@@H:45]([C:48]([CH3:50])=[CH2:49])[C@@H:14]1[C@@H:15]1[C@@:28]([CH3:31])([CH2:29][CH2:30]2)[C@@:27]2([CH3:32])[C@@H:18]([C@:19]3([CH3:44])[C@@H:24]([CH2:25][CH2:26]2)[C:23]([CH3:34])([CH3:33])[C:22]([C:35]2[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=2)=[CH:21][CH2:20]3)[CH2:17][CH2:16]1)=[O:11]>C1COCC1.CO.[OH-].[OH-].[Pd+2]>[O:51]=[S:2]1(=[O:1])[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[CH2:9][C:10]([NH:12][C@:13]12[CH2:47][CH2:46][C@@H:45]([CH:48]([CH3:49])[CH3:50])[C@@H:14]1[C@@H:15]1[C@@:28]([CH3:31])([CH2:29][CH2:30]2)[C@@:27]2([CH3:32])[C@@H:18]([C@:19]3([CH3:44])[C@@H:24]([CH2:25][CH2:26]2)[C:23]([CH3:34])([CH3:33])[C:22]([C:35]2[CH:36]=[CH:37][C:38]([C:39]([OH:41])=[O:40])=[CH:42][CH:43]=2)=[CH:21][CH2:20]3)[CH2:17][CH2:16]1)=[O:11]

Participants

5

Reactant 1

HCID 86701796HCID 86701796, compound

Product 1

HCID 86701795HCID 86701795, compoundYield 76.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)acetamido)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid (15 mg, 0.021 mmol) in a mixture of THF (4 mL) and MeOH (1 mL) under a N2 (g) atmosphere was added palladium hydroxide on carbon (3.67 mg, 5.23 μmol). The reaction mixture was purged with H2 (g) and was stirred under a H2 (g) atmosphere. After 6 h, the reaction mixture was filtered and washed with DCM and concentrated to give brown solid. The material was then plugged through a silica gel column (3 g), eluted with 90:10 DCM:MeOH, concentrated and dried to give 4-((1S,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-(2-((1S,4S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-yl)acetamido)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid (11.5 mg, 76% yield) as a light brown solid. LC/MS: m/e 719.3 (M+H)+, 2.61 min (method 3). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.90 (d, J=7.3 Hz, 2H), 7.30-7.21 (m, 1H), 7.18 (d, J=7.3 Hz, 2H), 5.28 (d, J=4.9 Hz, 1H), 4.09 (br. s., 1H), 3.77 (br. s., 1H), 3.65 (d, J=6.6 Hz, 2H), 2.59 (d, J=12.7 Hz, 4H), 2.32 (d, J=11.2 Hz, 1H), 2.13 (dd, J=17.0, 5.7 Hz, 1H), 1.97-1.82 (m, 3H), 1.78-1.67 (m, 3H), 1.60-1.42 (m, 12H), 1.39 (br. s., 1H), 1.24 (br. s., 4H), 1.13 (br. s., 1H), 1.07 (br. s., 3H), 1.00 (br. s., 6H), 0.92 (br. s., 6H), 0.88 (d, J=6.4 Hz, 3H), 0.78 (d, J=6.4 Hz, 3H).

Workup

  1. customThe reaction mixture was purged with H2 (g)
  2. filtrationthe reaction mixture was filtered
  3. washwashed with DCM
  4. concentrationconcentrated
  5. customto give brown solid
  6. washeluted with 90:10 DCM
  7. concentrationMeOH, concentrated
  8. customdried

Sources & evidence

ORD record
ord-40c23c1eb78448f2aa2f71848645e79b
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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