Methylamine → HCID 71584784, compound

HRID 1257261Notes

Reaction equation

HRID 1257261 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)=[CH:6][C:5]([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[N:33])[CH:27]=2)=[O:24])=[C:4]([F:34])[CH:3]=1.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=CC=CC=2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:71][NH2:72]>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]>[Cl:1][C:2]1[C:7]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:72][CH3:71])[CH:12]=3)=[CH:6][C:5]([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[N:33])[CH:27]=2)=[O:24])=[C:4]([F:34])[CH:3]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 86713684HCID 86713684, compound

Product 1

HCID 71584784HCID 71584784, compoundYield 15.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(4-chloro-5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-cyanophenyl)urea (0.210 g, 0.423 mmol), t-butyl X-Phos (0.020 g, 0.047 mmol), Pd2(dba)3 (0.020 g, 0.022 mmol), Cs2CO3 (0.400 g, 1.228 mmol) and methylamine (2.0M in THF, 4.0 mL, 8.0 mmol) in dioxane (5 mL) was heated at 90° C. for 5 h, then cooled to RT stirred overnight. The solids were removed via filtration, washed with DCM, then MeCN and the filtrate concentrated to dryness and purified via silica gel chromatography (EtOAc/DCM) to afford 1-(4-chloro-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3-cyanophenyl)urea (33 mg, 15% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.40 (s, 1H), 8.83 (s, 1H), 8.41 (s, 1H), 8.13 (d, J=8.6 Hz, 1H), 7.97 (t, J=1.8 Hz, 1H), 7.74 (s, 1H), 7.61-7.45 (m, 4H), 7.05 (d, J=5.1 Hz, 1H), 6.24 (s, 1H), 4.14 (d, J=7.4 Hz, 2H), 2.86 (d, J=4.9 Hz, 3H), 1.21 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 491.1 [M+H]+.

Workup

  1. temperaturecooled to RT
  2. customThe solids were removed via filtration
  3. washwashed with DCM
  4. concentrationMeCN and the filtrate concentrated to dryness
  5. custompurified via silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-a7e67abdb791410f8c38455912835e2a
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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