Water → (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamine

HRID 931645Notes

Reaction equation

HRID 931645 reaction equation
Cl[C:2]1[N:7]=[C:6]([F:8])[C:5]2[O:9][C:10]3[C:15]([C@@:16]4([CH2:21][CH2:20][O:19][C:18]([NH2:22])=[N:17]4)[C:4]=2[CH:3]=1)=[CH:14][C:13]([NH2:23])=[CH:12][CH:11]=3.[O:24]1[CH2:29][CH2:28][CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[O:24]1[CH2:29][CH2:28][CH:27]=[C:26]([C:2]2[N:7]=[C:6]([F:8])[C:5]3[O:9][C:10]4[C:15]([C@@:16]5([CH2:21][CH2:20][O:19][C:18]([NH2:22])=[N:17]5)[C:4]=3[CH:3]=2)=[CH:14][C:13]([NH2:23])=[CH:12][CH:11]=4)[CH2:25]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 158366332-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 90158687(S)-3-chloro-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamine

Product 1

HCID 117600889(S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamineYield 72%

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of (S)-3-chloro-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.354 g, 1.058 mmol), 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.667 g, 3.17 mmol), 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (0.037 g, 0.053 mmol) and potassium phosphate tribasic (0.673 g, 3.17 mmol) in dioxane/water (42 mL) was heated in microwave at 130° C. for 40 min. The mixture was poured into water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-5% 2M NH3 MeOH/DCM to afford (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.29 g, 0.758 mmol, 72% yield).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customchromatographed on silica gel using 0-5% 2M NH3 MeOH/DCM

Sources & evidence

ORD record
ord-e86609bedba348e78be50e895a833fcb
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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