Potassium Phosphate, Tribasic → (S)-N-(7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamide

HRID 455665Notes

Reaction equation

HRID 455665 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([N:20]=[C:19]([NH:21][CH:22]=[O:23])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12]([O:24][CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[F:30][C:31]1[C:36](B(O)O)=[CH:35][CH:34]=[CH:33][N:32]=1.P([O-])([O-])([O-])=O.[K+].[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>[F:30][C:31]1[C:36]([C:2]2[CH:3]=[C:4]3[C@:15]4([N:20]=[C:19]([NH:21][CH:22]=[O:23])[CH2:18][O:17][CH2:16]4)[C:14]4[CH:13]=[C:12]([O:24][CH2:25][C:26]([CH3:28])([CH3:29])[CH3:27])[N:11]=[CH:10][C:9]=4[O:8][C:5]3=[CH:6][CH:7]=2)=[CH:35][CH:34]=[CH:33][N:32]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27832702-Fluoropyridine-3-boronic acidHCID 86658384(S)-N-(7-bromo-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamide

Product 1

HCID 58465913(S)-N-(7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazine]-5'-yl)formamideYield 41.2%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)—N-(7-bromo-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazine]-5′-yl)formamide (0.075 g, 0.163 mmol), 2-fluoropyridin-3-ylboronic acid (0.046 g, 0.326 mmol), potassium phosphate (0.104 g, 0.489 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (5.77 mg, 8.15 μmol). The vial was flushed with Ar (g), then dioxane (0.611 mL) and water (0.204 mL) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 100° C. The reaction was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (0-10% MeOH:DCM w/1% NH4OH) to afford 32 mg of (S)—N-(7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazine]-5′-yl)formamide as an off-white solid.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (0.611 mL) and water (0.204 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. washthe combined organic layers were washed with brine
  8. dry with materialdried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified via column chromatography (0-10% MeOH:DCM w/1% NH4OH)

Sources & evidence

ORD record
ord-995c50a6fddb4ea592a51d88c1e7acd5
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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