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

반응식

HRID 530259 반응식
[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

참가 물질

9

반응물 4

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

생성물 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

시약·촉매·용매 4

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 21899815MeOH tetrahydrofuran용매

실험 절차

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]−.

후처리

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

출처 및 근거

ORD 기록
ord-5105359d8f0c471a8a34aa9d0538db85
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09353061B2

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