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

反応式

HRID 530259 の反応式
[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

参加物

9

反応物 4

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

生成物 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

試薬・触媒・溶媒 4

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

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]−.

後処理

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

出典と根拠

ORDレコード
ord-5105359d8f0c471a8a34aa9d0538db85
出典データセット
uspto-grants-2016_05
特許番号
US09353061B2

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