Nitrogen → HCID 90410175, compound

HRID 1848758Notes

Reaction equation

HRID 1848758 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=3)[CH:11]=[CH:10][C:9]=2[N+:23]([O-:25])=[O:24])=[C:4]([F:28])[CH:3]=1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.Cl.[F:63][C:64]1([F:68])[CH2:67][NH:66][CH2:65]1.N#N>>[F:63][C:64]1([F:68])[CH2:67][N:66]([C:2]2[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]3[CH:13]=[C:12]([O:14][CH2:15][C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][N:17]=4)[CH:11]=[CH:10][C:9]=3[N+:23]([O-:25])=[O:24])=[C:4]([F:28])[CH:3]=2)[CH2:65]1

Participants

5

Reactant 4

HCID 947NitrogenHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 90410749HCID 90410749, compound

Product 1

HCID 90410175HCID 90410175, compoundYield 61.1%

Procedure

To a sealable vial was added N-(4-bromo-2-fluorobenzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroaniline (700 mg, 1.57 mmol) RuPhos precatalyst (234 mg, 0.314 mmol) and RuPhos (149 mg, 0.314 mmol), 3,3-difluoroazetidine hydrochloride (610 mg, 4.71 mmol) and N2 sparged THF (7.84 mL) followed by LiHMDS (6.27 mL, 1.0 N in THF). The resulting mixture is stirred at RT for 3 min. The resulting mixture was partitioned between NH4Cl and EtOAc, the organic layer was separated, dried and concentrated to dryness. The residue was purified by FCC to provide the title compound (440 mg, 61%). MS (ESI): mass calcd. for C23H21F3N4O3, 458.16; m/z found, 459.1 [M+H]+.

Workup

  1. customsparged THF (7.84 mL)
  2. customThe resulting mixture was partitioned between NH4Cl and EtOAc
  3. customthe organic layer was separated
  4. customdried
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-18ef746a1cb9430483525419808d5726
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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