Dichloromethane → N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-6-fluorophenyl)acrylamide

HRID 58216Notes

Reaction equation

HRID 58216 reaction equation
[F:1][C:2]1[C:3]([N+:9]([O-])=O)=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].NC1C(C)=CC=CC=1N[C:21]1[N:26]=[CH:25][N:24]=[C:23]([N:27]([CH3:51])[C:28]([N:30]([C:39]2[C:44]([Cl:45])=[C:43]([O:46][CH3:47])[CH:42]=[C:41]([O:48][CH3:49])[C:40]=2[Cl:50])COCC[Si](C)(C)C)=[O:29])[CH:22]=1.C(N(C(C)C)CC)(C)C.[C:61](O)(=[O:64])[CH:62]=[CH2:63].C(Cl)Cl.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>>[Cl:50][C:40]1[C:41]([O:48][CH3:49])=[CH:42][C:43]([O:46][CH3:47])=[C:44]([Cl:45])[C:39]=1[NH:30][C:28](=[O:29])[N:27]([C:23]1[N:24]=[CH:25][N:26]=[C:21]([NH:5][C:4]2[CH:6]=[CH:7][CH:8]=[C:2]([F:1])[C:3]=2[NH:9][C:61](=[O:64])[CH:62]=[CH2:63])[CH:22]=1)[CH3:51]

Participants

7

Reactant 6

HCID 6344DichloromethaneHCID 6581Acrylic AcidHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 27828343-Fluoro-2-nitroanilineHCID 131736990HCID 131736990, compound

Product 1

HCID 118025871N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-6-fluorophenyl)acrylamideYield 71%

Procedure

The compound was synthesized following the approach outlined in Procedure 2G (Example 123), substituting 3-fluoro-2-nitroaniline in step (d), omitting step (e), and modifying step (g) to the following procedure: To a solution of 1-(6-((2-amino-3-methylphenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea (31 mg, 0.051 mmol), diisopropyl ethylamine (13.1 g, 0.103 mmol), and acrylic acid (39.9 g, 0.055 mmol) in DCM (1 ml, 15.54 mmol) was added a solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (48.1 g, 0.076 mmol, 50% solution EtOAc) at 0° C., and the resulting mixture was stirred at room temperature for 2 h. The mixture was concentrated and the residue was purified by silica gel column to obtain the SEM protected title compound (24 mg, yield: 71% in three steps). Following the final step (g), the title compound was isolated (12 mg, yield: 62%). 1H-NMR (400 MHz, CDCl3) δ 3.40 (s, 3H) 3.93 (m, 6H) 5.91 (d, 1H) 6.20 (s, 1H) 6.30-6.45 (m, 1H) 6.50-6.58 (m, 2H) 7.01 (t, 1H) 7.28-7.35 (m, 1H) 7.42-7.63 (m, 2H) 8.41 (s, 1H) 12.43 (br. s., 1H); ESI-MS: 535 [M+H]+.

Workup

  1. customThe compound was synthesized
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by silica gel column
  4. customto obtain the SEM

Sources & evidence

ORD record
ord-a9b9a92c2e324712847040b1e5285061
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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