Sodium Carbonate → HCID 86729628, compound

HRID 2284901Notes

Reaction equation

HRID 2284901 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[NH:16][C:17](=[O:20])[CH:18]=[CH2:19])[C:5]([Cl:21])=[CH:4][N:3]=1.NC1C=CC(F)=CC=1NC(=O)C=C.ClC1N=C(Cl)C(Cl)=CN=1.C(=O)([O-])[O-].[Na+].[Na+].[NH2:50][C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][C:59]=1[C:60]#[N:61])[C:54]([NH2:56])=[O:55].C1(P(N(C)C)C2C=CC=CC=2)C=CC=CC=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C>C(O)(CC)(C)C.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:17]([NH:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[NH:8][C:6]1[C:5]([Cl:21])=[CH:4][N:3]=[C:2]([NH:50][C:51]2[CH:52]=[C:53]([CH:57]=[CH:58][C:59]=2[C:60]#[N:61])[C:54]([NH2:56])=[O:55])[N:7]=1)(=[O:20])[CH:18]=[CH2:19]

Participants

10

Reactant 7

HCID 10340Sodium CarbonateHCID 2372592,4,5-TrichloropyrimidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 11333675HCID 11333675, compoundHCID 63257377HCID 63257377, compoundHCID 86729629HCID 86729629, compoundHCID 86729630HCID 86729630, compound

Product 1

HCID 86729628HCID 86729628, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
90 °C

Procedure

Compound I-207 was prepared according to the step described below. To a stirred solution of N-(2-((2,5-dichloropyrimidin-4-yl)amino)-5-fluorophenyl)acrylamide (200 mg, 0.613 mmol), which was prepared using N-(2-amino-5-fluorophenyl)acrylamide and 2,4,5-trichloropyrimidine in a method similar to step 1 of Example 162, in tert-amyl alcohol (5 mL) was added aqueous sodium carbonate (96 mg, 0.905 mmol), 3-amino-4-cyanobenzamide (100 mg, 0.324 mmol) and diphenylphosphino-N,N-dimethylamine (125 mg, 0.919 mmol). The mixture was degassed for 20 min. To this mixture, Pd2(dba)3 (625 mg, 0.733 mmol) and Davephos (96 mg, 0.244 mmol) were added and again degassed for 10 min. The reaction mixture was heated to 90° C. for 2 h. TLC showed completion of starting material. The crude mixture was purified by silica gel column chromatography followed by preparative HPLC to yield 30 mg of the title compound. MS m/z: 452.1 (ES+, M+H); 1HNMR (DMSO-d6) δ 5.77-5.80 (dd, 1H J=2.0 Hz and 10.2 Hz), 6.26-6.31 (dd, 1H J=1.9 Hz and 17 Hz), 6.46-6.52 (dd, 1H J=10.2, 17 Hz), 6.90-6.95 (dt, 3.0, 8.4 Hz), 7.38-7.41 (dd, 1H J=3.0, 10.4 Hz), 7.56-7.64 (m, 3H), 7.78 (d, 1H J=8.1 Hz), 7.96 (d, 1H J=1.2 Hz), 8.10-8.12 (m, 2H), 8.5 (s, 1H), 9.4 (s, 1H), 10.02 (s, 1H). MS m/z: 452.1 (ES+, M+H).

Workup

  1. customCompound I-207 was prepared
  2. customThe mixture was degassed for 20 min
  3. customagain degassed for 10 min
  4. customThe crude mixture was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-eb352fcc307f45fd86322cd66e00b4ca
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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