Potassium Carbonate → (S)-tert-butyl 7-((3-methyloxetan-3-yl)ethynyl)-3-(6-methylpyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamate

HRID 335942Notes

Reaction equation

HRID 335942 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][S:18][C:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:28]#[C:29][C:30]4([CH3:34])[CH2:33][O:32][CH2:31]4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[CH3:35][C:36]1[N:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>>[CH3:34][C:30]1([C:29]#[C:28][C:12]2[CH:13]=[C:14]3[C@@:15]4([CH2:19][S:18][C:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[N:16]4)[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:39]5[CH:40]=[N:41][C:36]([CH3:35])=[CH:37][CH:38]=5)[CH:3]=4)[O:8][C:9]3=[CH:10][CH:11]=2)[CH2:31][O:32][CH2:33]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 67437931(S)-tert-butyl 3-bromo-7-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamate

Product 1

HCID 67436896(S)-tert-butyl 7-((3-methyloxetan-3-yl)ethynyl)-3-(6-methylpyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamateYield 49%

Conditions

Temperature
80 °C

Procedure

A vial was charged with (S)-tert-butyl 3-bromo-7-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazole]-2′-ylcarbamate (0.054 g, 0.10 mmol), 6-methylpyridin-3-ylboronic acid (0.041 g, 0.30 mmol), potassium carbonate (0.069 g, 0.50 mmol), and Pd(AmPhos)2Cl2 (7.05 mg, 9.95 μmol). The vial was flushed with Ar (g), then dioxane (0.66 mL) and water (0.33 mL) were added in sequence. The vial was sealed and heated at 80° C. for 16 h. The reaction was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography on silica gel (0-75% EtOAc:Hex) to afford (S)-tert-butyl 7-((3-methyloxetan-3-yl)ethynyl)-3-(6-methylpyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazole]-2′-ylcarbamate (0.027 g, 0.049 mmol, 48.9% yield) as a white solid. MS m/z=555.3 [M+H]+. Calculated for C31H30N4O4S: 554.20.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (0.66 mL) and water (0.33 mL) were added in sequence
  3. customThe vial was sealed
  4. additionThe reaction was diluted with EtOAc
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with EtOAc
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography on silica gel (0-75% EtOAc:Hex)

Sources & evidence

ORD record
ord-1cc87b8b00374c05859c26a108bff38e
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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