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 1487489Notes

Reaction equation

HRID 1487489 reaction equation
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]

Participants

7

Reactant 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

Product 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 esterYield 60.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-866d90689fac4d37b598946ec71f30ea
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

Loading…