Potassium Carbonate → tert-butyl 3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamate

HRID 335843Notes

Reaction equation

HRID 335843 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]4[C:29]([F:34])=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.[O:35]1[CH2:40][CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH2:37][CH2:36]1.C(=O)([O-])[O-].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[O:35]1[CH2:36][CH:37]=[C:38]([C:2]2[CH:3]=[C:4]3[C:15]4([CH2:19][S:18][C:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[N:16]4)[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([C:28]5[C:29]([F:34])=[N:30][CH:31]=[CH:32][CH:33]=5)[CH:13]=4)[O:8][C:5]3=[N:6][CH:7]=2)[CH2:39][CH2:40]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 67382904tert-butyl 3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamate

Product 1

HCID 67383473tert-butyl 3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazole]-2'-ylcarbamate

Reagents, catalysts & solvents 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Catalyst

Conditions

Temperature
80 °C

Procedure

A vial was charged with tert-butyl 3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazole]-2′-ylcarbamate (0.105 g, 0.193 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.122 g, 0.580 mmol), potassium carbonate (0.134 g, 0.966 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.014 g, 0.019 mmol). The vial was flushed with Ar (g), then dioxane (1.288 mL) and water (0.644 mL) were added in sequence. The vial was sealed and heated at 80° C. overnight. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel chromatography (gradient elution 0-100% EtOAc:Hex) to afford tert-butyl 3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazole]-2′-ylcarbamate as an off-white solid. MS m/z=547.2. Calc'd for C29H27FN4O4S: 546.61.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (1.288 mL) and water (0.644 mL) were added in sequence
  3. customThe vial was sealed
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via silica gel chromatography (gradient elution 0-100% EtOAc:Hex)

Sources & evidence

ORD record
ord-b2545adb3e52463f94e892512a145a83
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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