Water → (4S,5R)-4-Fluoromethyl-5-{4-[2-(methanesulfonylamino-methyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 525557ノート

反応式

HRID 525557 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([CH2:11][NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:10]=[C:4]2[CH:3]=1.[C:17]([O:21][C:22]([N:24]1[C@H:28]([CH2:29][F:30])[C@@H:27]([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)[O:26][C:25]1([CH3:47])[CH3:46])=[O:23])([CH3:20])([CH3:19])[CH3:18].O.C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:17]([O:21][C:22]([N:24]1[C@H:28]([CH2:29][F:30])[C@@H:27]([C:31]2[CH:32]=[CH:33][C:34]([C:2]3[CH:7]=[CH:6][N:5]4[CH:8]=[C:9]([CH2:11][NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[N:10]=[C:4]4[CH:3]=3)=[CH:35][CH:36]=2)[O:26][C:25]1([CH3:47])[CH3:46])=[O:23])([CH3:20])([CH3:18])[CH3:19]

参加物

7

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylateHCID 86695441N-(7-Bromo-imidazo[1,2-a]pyridin-2-ylmethyl)-methane sulfonamide

生成物 1

HCID 86695442(4S,5R)-4-Fluoromethyl-5-{4-[2-(methanesulfonylamino-methyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester収率 60.4%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

To the solution of N-(7-Bromo-imidazo[1,2-a]pyridin-2-ylmethyl)-methane sulfonamide (71 mg. 0.233 mmol) and (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (111 mg, 0.256 mmol) in dimethoxyethane:water (2.2 mL:0.5 mL) in a microwave tube is added Na2CO3 (62 mg, 0.583 mmol) at room temperature. The resulting reaction mixture is degassed with nitrogen for 30 minutes then added Pd(PPh3)2Cl2 (9 mg, 0.0116 mmol) and heated in microwave at 120° C. for 2 hours. The solvent is evaporated and purified by flash column chromatography eluting in 2% methanol in CH2Cl2 to afford the title compound (75 mg). 1H-NMR (400 MHz, DMSO-d6) δ: 1.44 (s, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 2.92 (s, 3H), 3.83-3.89 (m, 1H), 4.28 (d, J=6.12 Hz, 2H), 4.45-4.55 (m, 1H), 4.65-4.75 (m, 1H), 5.13 (d, J=7.2 Hz, 1H), 7.27-7.29 (dd, J1=1.6 Hz, J2=7.20 Hz, 1H), 7.56-7.58 (m, 3H), 7.82-7.88 (m, 4H), 8.61 (d, J=7.2 Hz, 1H). LC-MS (m/z): [M+H]=533.1.

後処理

  1. customThe resulting reaction mixture
  2. customis degassed with nitrogen for 30 minutes
  3. customThe solvent is evaporated
  4. custompurified by flash column chromatography
  5. washeluting in 2% methanol in CH2Cl2

出典と根拠

ORDレコード
ord-c4f465ad97064307977149491b2a92d8
出典データセット
uspto-grants-2016_05
特許番号
US09340564B2

反応ノート

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