1-Hydroxybenzotriazole → {4-[(2beta,3alpha,17beta)-3-hydroxy-17-methoxyandrostan-2-yl]piperazin-1-yl}[(2S)-1-(naphthalen-2-ylcarbonyl)pyrrolidin-2-yl]methanone

HRID 244256Notes

Reaction equation

HRID 244256 reaction equation
[CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[CH:12]([CH2:13][C@H:14]([OH:28])[C@@H:15]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:16]1)[CH2:11][CH2:10]3.[C:29]1([C:39]([N:41]2[CH2:48][CH2:47][CH2:46][C@H:42]2[C:43]([OH:45])=O)=[O:40])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][CH:30]=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>[OH:28][C@@H:14]1[C@@H:15]([N:22]2[CH2:23][CH2:24][N:25]([C:43]([C@@H:42]3[CH2:46][CH2:47][CH2:48][N:41]3[C:39]([C:29]3[CH:30]=[CH:31][C:32]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:38]=3)=[O:40])=[O:45])[CH2:26][CH2:27]2)[CH2:16][C@@:17]2([CH3:18])[CH:12]([CH2:11][CH2:10][C@@H:9]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH3:5])[C@H:6]3[CH2:7][CH2:8][C@@H:3]2[O:2][CH3:1])[CH2:13]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 104921841-(Naphthalene-1-ylcarbonyl)-L-ProlineHCID 86660501(2beta,3alpha,17beta)-17-Methoxv-2-(piperazin-1-yl)androstan-3-ol

Product 1

HCID 86660502{4-[(2beta,3alpha,17beta)-3-hydroxy-17-methoxyandrostan-2-yl]piperazin-1-yl}[(2S)-1-(naphthalen-2-ylcarbonyl)pyrrolidin-2-yl]methanoneYield 23.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of compound 36 (90 mg, 0.23 mmol) in anhydrous DMF (5 mL) at room temperature under an atmosphere of argon were added carboxylic acid 20 (68 mg, 0.25 mmol), PyBOP (132 mg, 0.25 mmol), HOBt (34 mg, 0.25 mmol), and DIPEA (128 μL, 0.74 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 two successive flash chromatography procedures using (DCM/MeOH: 95:5) and (Hexanes/Acetone: 1:1) respectively and trituration with diethyl ether yielded 35 mg (23%) of compound 37. 1H NMR (CDCl3) δ: 0.73 (s, 18-CH3), 0.84 (s, 19-CH3), 0.65-2.25 (residual CH and CH2), 2.40-2.75 (broad m, 2×CH2N and 2α-CH), 3.19 (t, J=8.3 Hz, 17α-CH), 3.32 (s, OCH3), 3.45-3.95 (broad m, 2×CH2NCO, CH2N of proline and 3β-CH), 5.14 (t, J=7.6 Hz, NCHCO of proline), 7.52 (m, 2×CH of naphthalene), 7.67 (d, J=8.4 Hz, CH of naphthalene), 7.85 (m, 3×CH of naphthalene), 8.09 (s, CH of naphthalene). 13C NMR (CDCl3) δ: 11.7, 17.1, 21.0, 23.2, 27.6, 28.1, 29.4, 33.0, 35.2, 35.8, 38.4, 43.0, 48.0, 49.0, 50.3, 51.1, 55.7, 56.0, 56.2, 57.8, 59.3, 63.6, 63.8, 64.1, 64.7, 65.0, 66.9, 90.7, 126.6, 127.2, 127.4, 127.7, 127.8, 128.0, 128.6, 132.5, 133.6, 133.9, 169.5, 170.4 HRMS: calcd for C40H55N3O4: 642.4265, found [M+H]+ 642.4274.

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 two successive flash chromatography procedures

Sources & evidence

ORD record
ord-2f4ef005921a4147a0364c4ee6712398
Source dataset
uspto-grants-2014_02
Patent number
US08653054B2

Reaction notes

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