Magnesium Bromide → (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-isopropyl pyrimidin-5-yl]-3,5-dihydroxy-N-hydroxy-6-heptenamide

HRID 530259

Reaction equation

HRID 530259 reaction equation
[CH3:1][CH:2]([C:4]1[N:9]=[C:8]([N:10]([S:12]([CH3:15])(=[O:14])=[O:13])[CH3:11])[N:7]=[C:6]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[C:5]=1/[CH:23]=[CH:24]/[C@@H:25]([OH:33])[CH2:26][C@@H:27]([OH:32])[CH2:28][C:29](O)=[O:30])[CH3:3].[Mg+2].[Br-].[Br-].Cl.[NH2:38][OH:39].C(=O)(O)[O-].[Na+]>C1COCC1.CO.C(Cl)Cl.CCOC(C)=O.CC#N>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:6]2[C:5](/[CH:23]=[CH:24]/[C@@H:25]([OH:33])[CH2:26][C@@H:27]([OH:32])[CH2:28][C:29]([NH:38][OH:39])=[O:30])=[C:4]([CH:2]([CH3:3])[CH3:1])[N:9]=[C:8]([N:10]([CH3:11])[S:12]([CH3:15])(=[O:13])=[O:14])[N:7]=2)=[CH:17][CH:18]=1

Participants

9

Reactant 4

HCID 82241Magnesium BromideHCID 443297Hydroxyamine hydrochlorideHCID 446157RosuvastatinHCID 516892Sodium Bicarbonate

Product 1

HCID 71655139(3R,5S,6E)-7-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-isopropyl pyrimidin-5-yl]-3,5-dihydroxy-N-hydroxy-6-heptenamide

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

By a procedure similar to Lova-HA, rosuvastatin (68 mg, 0.15 mmol, in the lactone form) was treated with MgBr2 (54 mg, 0.29 mmol), hydroxylamine hydrochloride (87 mg, 1.25 mmol), and sodium bicarbonate (99 mg, 1.18 mmol) in anhydrous THF/MeOH (7:3, 647 L) at ambient temperature for 6 h to give Rosuva-HA (37 mg, 51%). The purity was 97% as shown by HPLC analysis on an HC—C18 column (Agilent, 4.6×250 mm, 5 am), tR=13.8 min (gradients of 25-80% aqueous CH3CN in 30 min). C22H29FN4O6S; colorless oil; [α]24D=−1.1 (EtOAc, c=1.0); TLC (CH2Cl2/McOH (9:1)) Rf=0.35; IR νmax (neat) 3326, 2925, 2853, 1737, 1660, 1604, 1546, 1510, 1437, 1381, 1336, 1230, 1153, 1069, 965, 901, 845, 776 cm1; 1H NMR (DMSO-d6, 400 MHz) δ 10.32 (1H, br s), 8.70 (1H, br s), 7.71-7.74 (2H, m), 7.30 (2H, t, J=8.8 Hz), 6.50 (1H, dd, J=1.2, 16.2 Hz), 5.54 (1H, dd, J=5.6, 16.2 Hz), 4.94 (1H, d, J=4.4 Hz), 4.70 (1H, d, J=4.8 Hz), 4.19-4.22 (1H, m), 3.88 (1H, br s), 3.55 (3H, s), 3.41-3.48 (4H, m), 2.05 (2H, d, J=6.4 Hz), 1.48-1.56 (1H, m), 1.37-1.43 (1H, m), 1.22 (6H, d, J=6.8 Hz) ppm; 13C NMR (DMSO-d6, 100 MHz) δ 174.8, 167.9, 164.3, 163.3, 161.8, 157.3, 141.7, 134.9, 134.8, 132.6, 132.5, 122.2, 121.9, 115.6, 115.4, 69.1, 65.6, 44.6, 42.0, 41.2, 33.7, 31.7, 22.0 (2×) ppm; ESI-HRMS (negative mode) calcd. for C33H35FN3O5: 572.2561. found: m/z 572.2562 [M−H]−.

Workup

  1. customto give Rosuva-HA (37 mg, 51%)

Sources & evidence

ORD record
ord-5105359d8f0c471a8a34aa9d0538db85
Source dataset
uspto-grants-2016_05
Patent number
US09353061B2

Linked notes

Loading…