Atorvastatin → HCID 71655138, compound

HRID 530258Notes

Reaction equation

HRID 530258 reaction equation
[CH3:1][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15](O)=[O:16])[C:7]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:5]=1[C:33]([NH:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:34])[CH3:3].[Mg+2].[Br-].[Br-].Cl.[NH2:46][OH:47].C(=O)(O)[O-].[Na+]>C1COCC1.CO.C(Cl)Cl.CO.CCOC(C)=O.CC#N>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:7]2[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([NH:46][OH:47])=[O:16])[C:4]([CH:2]([CH3:3])[CH3:1])=[C:5]([C:33](=[O:34])[NH:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:6]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:25][CH:24]=1

Participants

9

Reactant 4

HCID 60823AtorvastatinHCID 82241Magnesium BromideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 71655138HCID 71655138, compound

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

By a procedure similar to Lova-HA, atorvastatin (168 mg, 0.31 mmol, in the lactone form) was treated with MgBr2 (115 mg, 0.62 mmol), hydroxylamine hydrochloride (184 mg, 2.6 mmol), and sodium bicarbonate (209 mg, 2.5 mmol) in anhydrous THF/MeOH (7:3, 1 mL) at ambient temperature for 20 h to give Atorva-HA (91 mg, 51%). The purity was 95% as shown by HPLC analysis on an HC—C18 column (Agilent, 4.6×250 mm, 5 Gm), tR=14.8 min (gradients of 30-100% aqueous CH3CN in 30 min). C33H36FN3O5; colorless oil; [α]26D=−1.3 (EtOAc, c=1.0); TLC (CH2Cl2/MeOH (9:1)) Rf=0.33; IR νmax (neat) 3405, 3301, 3059, 2960, 2926, 1738, 1657, 1595, 1527, 1508, 1436, 1314, 1241, 1223, 1157, 1108, 1078, 1046, 843, 753, 692 cm−1; 1H NMR (DMSO-d6, 400 MHz) δ 10.31 (1H, br s), 9.77 (1H, br s), 8.68 (1H, br s), 7.50 (2H, d, J=7.6 Hz), 7.18-7.24 (6H, m), 7.07 (4H, br s), 6.98-7.00 (2H, m), 4.69 (1H, br s), 4.60 (1H, d, J=4.0 Hz), 3.92-3.95 (1H, m), 3.72-3.83 (2H, m), 3.53 (1H, br s), 3.21-3.25 (1H, m), 2.01 (2H, d, J=6.0 Hz), 1.63 (1H, br s), 1.53 (1H, br s), 1.28-1.38 (8H, m) ppm; 13C NMR (DMSO-d6, 100 MHz) δ 167.4, 166.1, 162.8, 160.3, 139.4, 135.9, 134.9, 133.4, 129.1 (2×), 128.7, 128.4 (2×), 127.6 (2×), 127.3, 125.3, 122.9, 120.6, 119.4 (2×), 117.5, 115.4, 115.2, 66.0, 65.6, 43.8, 40.9, 40.7, 25.6, 22.3 (2×) ppm; ESI-HRMS (negative mode) calcd. for C33H35FN3O5: 572.2561. found: m/z 572.2562 [M−H]−.

Workup

  1. customto give Atorva-HA (91 mg, 51%)

Sources & evidence

ORD record
ord-07254714d9b445ed9a975cc3deef11b3
Source dataset
uspto-grants-2016_05
Patent number
US09353061B2

Reaction notes

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