1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → {4-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-ylamino]-pyrimidin-2-yl}-carbamic acid tert-butyl ester

HRID 2409236Notes

Reaction equation

HRID 2409236 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[C:20]([O:24][C:25](=[O:34])[NH:26][C:27]1[N:32]=[C:31]([NH2:33])[CH:30]=[CH:29][N:28]=1)([CH3:23])([CH3:22])[CH3:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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]>[C:20]([O:24][C:25](=[O:34])[NH:26][C:27]1[N:32]=[C:31]([NH:33][C:2]2[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=3[F:19])[CH:3]=2)[CH:30]=[CH:29][N:28]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18753326tert-Butyl (4-aminopyrimidin-2-yl)carbamateHCID 533447244-Chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

Product 1

HCID 53372717{4-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-ylamino]-pyrimidin-2-yl}-carbamic acid tert-butyl esterYield 27.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

200 mg 4-chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine (cf. EXAMPLE 1) and 143 mg (4-amino-pyrimidin-2-yl)-carbamic acid tert-butyl ester in 8 ml dioxane containing 444 mg Cs2CO3, 13 mg Pd2(dba)3 and 16 mg xantphos were incubated under argon gas at 80° C. for 16 hrs. After evaporation to dryness the crude sample was flashed on SiO2 with a MeOH gradient in DCM. A pooled fraction was dried down and digested with ether to give 88 mg product {4-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-ylamino]-pyrimidin-2-yl}-carbamic acid tert-butyl ester as a white powder with Rt˜1.80 min and correct mass found M+H˜467.

Workup

  1. customAfter evaporation to dryness the crude sample
  2. customA pooled fraction was dried down

Sources & evidence

ORD record
ord-15836f0441734b55a36473e433d92c20
Source dataset
uspto-grants-2014_08
Patent number
US08815893B2

Reaction notes

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