Sodium Carbonate → (S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(2'-hydroxy-5'-methyl-[1,1'-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HRID 1482005Notes

Reaction equation

HRID 1482005 reaction equation
[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=4)[N:19]=[C:15]3[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[OH:39][C:40]1[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][C:41]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:41]5[CH:42]=[C:43]([CH3:46])[CH:44]=[CH:45][C:40]=5[OH:39])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 18617005(2-Hydroxy-5-methylphenyl)boronic acidHCID 118308811(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118308900(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(2'-hydroxy-5'-methyl-[1,1'-biphenyl]-3-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateYield 58%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (84 mg, 0.144 mmol, 1 equiv) and (2-hydroxy-5-methylphenyl)boronic acid (33 mg, 0.216 mmol, 1.5 equiv) in DMF (1.4 mL, sparged with nitrogen for 10 min) was added Pd(PPh3)4 (17 mg, 0.014 mmol, 0.1 equiv) and 2 M Na2CO3 (0.144 mL, 0.287 mmol, 2 equiv). The reaction was heated at 90° C. for 3 h. Upon cooling to ambient temperature, the reaction was diluted with EtOAc, washed with water, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (51 mg, 58%) as a yellow foam. 1H NMR (400 MHz, CDCl3) δ 8.13 (br. s., 1H), 8.08-8.01 (m, J=7.0 Hz, 1H), 7.95 (br. s., 1H), 7.62-7.56 (m, 1H), 7.51 (br. s., 1H), 7.14 (s, 1H), 7.09 (d, J=8.3 Hz, 1H), 7.01 (s, 1H), 6.96 (d, J=7.5 Hz, 1H), 6.10-5.94 (m, 2H), 5.40 (d, J=17.1 Hz, 1H), 5.03 (d, J=9.5 Hz, 1H), 3.99 (d, J=5.0 Hz, 2H), 3.90 (br. s., 1H), 3.79-3.75 (m, 1H), 3.71 (s, 3H), 3.08 (br. s., 1H), 2.79-2.70 (m, 1H), 2.56 (br. s., 3H), 2.35 (s, 3H), 2.00 (d, J=13.6 Hz, 2H), 1.88-1.77 (m, 2H), 1.34 (s, 3H), 1.26 (s, 9H); LCMS (ESI, M+1): 612.4.

Workup

  1. temperatureUpon cooling to ambient temperature
  2. washwashed with water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane)

Sources & evidence

ORD record
ord-13f2c1393d1d4c73a8784d8d7cb7bc47
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

Loading…