10376-50-8 → HCID 50923234, compound

HRID 2179798Notes

Reaction equation

HRID 2179798 reaction equation
[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:34])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:33])[CH2:12][CH2:13][C@@:14]3([C:30](O)=[O:31])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:36])[CH3:35])(=[O:3])[CH3:2].[NH2:37][C@@H:38]1[CH2:41][C@H:40]([C:42]([N:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)=[O:43])[C:39]1([CH3:50])[CH3:49]>C(Cl)Cl>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:34])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:33])[CH2:12][CH2:13][C@@:14]3([C:30](=[O:31])[NH:37][C@@H:38]4[CH2:41][C@H:40]([C:42]([N:44]5[CH2:48][CH2:47][CH2:46][CH2:45]5)=[O:43])[C:39]4([CH3:50])[CH3:49])[CH2:26][CH2:25][C@@H:24]([C:27]([CH3:29])=[CH2:28])[C@@H:15]32)[C:6]1([CH3:36])[CH3:35])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 1030053410376-50-8HCID 58111068HCID 58111068, compound

Product 1

HCID 50923234HCID 50923234, compoundYield 76.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (0.336 g, 0.674 mmol) (Prepared as described in J. Med. Chem. 2009. 52, 3248-3258) in DCM (1 ml) Oxolyl chloride (0.58 ml, 6.746 mmol) in DCM (3.15 ml) was added at 0° C. and stirred at room temperature for about 3 hours and completion of the reaction monitored by TLC then the solvent was evaporated under nitrogen atmosphere and dissolved in DCM (4 ml), which was added to the above stirred solution of ((1S,3R)-3-amino-2,2-dimethylcyclobutyl)(pyrrolidin-1-yl)methanone (step 2, 0.264 g, 1.349 mmol) at 0° C. and allowed to stir at room temperature for about 16 hours. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with DCM and washed with aqueous 1N HCl, then washed with water and brine, and dried over Na2SO4, the solvent was evaporated and purified by silica gel column (100-200 mesh, elution 15% EtOAc in hexane) to afford the title compound as an off white solid. Wt: 0.350 g: Yield: 76.7%; 1H NMR (300 MHz, CDCl3): δ 6.28 (d, 1H), 4.72 (s, 1H), 4.58 (s, 1H), 4.51-4.06 (m, 2H), 3.56-3.27 (m, 8H), 3.18-3.08 (m, 1H), 2.91-2.74 (m, 2H), 2.60-2.46 (m, 2H), 2.37-2.20 (m, 3H), 2.08 (s, 3H), 1.99-1.11 (m, 26H), 1.00-0.75 (s, 18H); Mass: [M+Na]+ 699 (100%); IR (KBr, cm−1): 3268, 3077, 2955, 2873, 1734, 1716, 1618, 1549, 1455, 1452, 1371, 1344, 1242, 1180, 1150, 1033, 980, 869; M.R: 94.9° C.-101.2° C.

Workup

  1. customthe solvent was evaporated under nitrogen atmosphere
  2. dissolutiondissolved in DCM (4 ml)
  3. stirringto stir at room temperature for about 16 hours
  4. customAfter completion of the reaction (monitored by TLC)
  5. washwashed with aqueous 1N HCl
  6. washwashed with water and brine
  7. dry with materialdried over Na2SO4
  8. customthe solvent was evaporated
  9. custompurified by silica gel column (100-200 mesh, elution 15% EtOAc in hexane)

Sources & evidence

ORD record
ord-93508bd5780c4b75b70015e7aa7768b6
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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