Lithium Hexamethyldisilazide → HCID 178507231, compound

HRID 931640Notes

Reaction equation

HRID 931640 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.C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1.C[Si]([N-:61][Si](C)(C)C)(C)C.[Li+]>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].C1COCC1>[NH2:61][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

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 178522499HCID 178522499, compound

Product 1

HCID 178507231HCID 178507231, compound

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

A microwave vial was charged with (S,Z)—N-(7-bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazinan]-2′-ylidene)benzamide (2.0 g, 3.98 mmol), Pd(dba)2 (0.073 g, 0.080 mmol) and (2-biphenyl)dicyclohexylphosphine (0.067 g, 0.191 mmol), sealed and purged with N2 followed by the addition of THF (2 mL) and lithium bis(trimethylsilyl)amide, 1.0 m solution in tetrahydrofuran (8.75 ml, 8.75 mmol). The resulting mixture was heated at 65° C. for 17 h, quenched with saturated NH4Cl. The mixture was diluted with EtOAc, washed with water, brine, and dried over Na2SO4. The solution was concentrated and chromatographed on silica gel using 0-100% EtOAc/hexanes to afford a yellow oil as (S,Z)—N-(7-amino-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazinan]-2′-ylidene)benzamide.

Workup

  1. customsealed
  2. custompurged with N2
  3. customquenched with saturated NH4Cl
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. concentrationThe solution was concentrated
  8. customchromatographed on silica gel using 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-2937724073ef453080c308c2e3df31e0
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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