2-Amino-3-methylpyridine → HCID 178426305, compound

HRID 931648Notes

Reaction equation

HRID 931648 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:20][CH2:19][O:18]/[C:17](=[N:21]\[C:22](=[O:29])[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)/[NH:16]3)[C:14]3[CH:13]=[C:12]([Cl:30])[N:11]=[C:10]([F:31])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[NH2:32][C:33]1[C:38]([CH3:39])=[CH:37][CH:36]=[CH:35][N:34]=1.C(P(C(C)(C)C)C1(CCC)CC(CCC)=CC(CCC)=C1C1C=CC=CC=1)(C)(C)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:30][C:12]1[N:11]=[C:10]([F:31])[C:9]2[O:8][C:5]3[C:4]([C@@:15]4([CH2:20][CH2:19][O:18]/[C:17](=[N:21]\[C:22](=[O:29])[C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=5)/[NH:16]4)[C:14]=2[CH:13]=1)=[CH:3][C:2]([NH:32][C:33]1[C:38]([CH3:39])=[CH:37][CH:36]=[CH:35][N:34]=1)=[CH:7][CH:6]=3

Participants

8

Reactant 4

HCID 153472-Amino-3-methylpyridineHCID 2733832Lithium HexamethyldisilazideHCID 1317351732-Di-t-butylphosphino-2,4,6-tri-1-propyl-1,1-biphenylHCID 178522499HCID 178522499, compound

Product 1

HCID 178426305HCID 178426305, compoundYield 26.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S,Z)—N-(7-bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazinan]-2′-ylidene)benzamide (0.25 g, 0.497 mmol), 2-amino-3-picoline (0.055 ml, 0.547 mmol), pd2(dba)3 (0.023 g, 0.025 mmol) and 2-di-t-butylphosphino-2,4,6-tri-1-propyl-1,1-biphenyl (0.037 g, 0.087 mmol) was purged with N2 followed by the addition of toluene (2 mL) and lithium bis(trimethylsilyl)amide (1.243 ml, 1.243 mmol). The resulting mixture was heated at 100° C. and after 30 min the reaction was cooled, diluted with EtOAc and washed with saturated NH4Cl. The organic phase was dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-100% EtOAc/hexanes. The product was repurified by HPLC to afford (S,Z)—N-(3-chloro-1-fluoro-7-((3-methylpyridin-2-yl)amino)spiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazinan]-2′-ylidene)benzamide (0.069 g, 0.130 mmol, 26% yield).

Workup

  1. customwas purged with N2
  2. temperaturewas cooled
  3. washwashed with saturated NH4Cl
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on silica gel using 0-100% EtOAc/hexanes
  8. customThe product was repurified by HPLC

Sources & evidence

ORD record
ord-daad18fa185c49a69fb579525e960078
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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