1-Hydroxybenzotriazole → Androstan-17-one

HRID 244250Notes

Reaction equation

HRID 244250 reaction equation
O[C@@H:2]1[C@@H:19](N2CCNCC2)[CH2:18][C@@:17]2([CH3:26])[CH:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH2:10][C:11]2=[O:27])[CH2:3]1.C1(C(N2CCC[C@H]2C(O)=O)=O)C2C(=CC=CC=2)C=CC=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:13][C@:12]12[CH2:14][CH2:15][C@H:16]3[C@@H:7]([CH2:6][CH2:5][CH:4]4[C@:17]3([CH3:26])[CH2:18][CH2:19][CH2:2][CH2:3]4)[C@@H:8]1[CH2:9][CH2:10][C:11]2=[O:27]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 104921841-(Naphthalene-1-ylcarbonyl)-L-ProlineHCID 86660495(2beta,3alpha)-3-Hydroxy-2-(piperazin-1-yl)androstan-17-one

Product 1

HCID 10880319Androstan-17-oneYield 143%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 23 (150 mg, 0.40 mmol) in anhydrous DMF (7 mL) at room temperature under an atmosphere of argon were added carboxylic acid 20 (119 mg, 0.44 mmol), PyBOP (229 mg, 0.44 mmol), HOBt (60 mg, 0.44 mmol), and DIPEA (220 μL, 1.26 mmol). The solution was subsequently stirred overnight at room temperature. The resulting solution was then poured into water and extracted with EtOAc (2×30 mL), washed with brine, dried with MgSO4 and evaporated to dryness. Purification by flash chromatography (Hexanes/Acetone: 1:1) yielded 157 mg (63%) of compound 24. 1H NMR (CDCl3) δ: 0.89 (s, 18-CH3 and 19-CH3), 0.70-2.50 (residual CH and CH2), 3.45-3.90 (broad, NCH2 of proline and 2×CH2NCO), 3.95 (m, 3β-CH), 5.09 (broad, NCHCO of proline), 7.55 (m, 2×CH of naphthalene), 7.61 (m, CH of naphthalene), 7.87 (m, 3×CH of naphthalene), 8.06 (s, CH of naphthalene).

Workup

  1. extractionextracted with EtOAc (2×30 mL)
  2. washwashed with brine
  3. dry with materialdried with MgSO4
  4. customevaporated to dryness
  5. customPurification by flash chromatography (Hexanes/Acetone: 1:1)

Sources & evidence

ORD record
ord-d5aadd263c2744ed9c06e55402641ec2
Source dataset
uspto-grants-2014_02
Patent number
US08653054B2

Reaction notes

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