Trifluoroacetic acid → N-(5-(4-(2-aminoethyl)piperazin-1-yl)-2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide

HRID 58210Notes

Reaction equation

HRID 58210 reaction equation
[C:1]([NH:5][C:6]1[CH:11]=[C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][NH:20]C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH:9]=[CH:8][C:7]=1[N:28]([C:36]1[CH:41]=[C:40]([N:42]([CH3:66])[C:43]([N:45]([C:54]2[C:59]([Cl:60])=[C:58]([O:61][CH3:62])[CH:57]=[C:56]([O:63][CH3:64])[C:55]=2[Cl:65])COCC[Si](C)(C)C)=[O:44])[N:39]=[CH:38][N:37]=1)C(=O)OC(C)(C)C)(=[O:4])[CH:2]=[CH2:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:20][CH2:19][CH2:18][N:15]1[CH2:16][CH2:17][N:12]([C:10]2[CH:9]=[CH:8][C:7]([NH:28][C:36]3[CH:41]=[C:40]([N:42]([CH3:66])[C:43]([NH:45][C:54]4[C:59]([Cl:60])=[C:58]([O:61][CH3:62])[CH:57]=[C:56]([O:63][CH3:64])[C:55]=4[Cl:65])=[O:44])[N:39]=[CH:38][N:37]=3)=[C:6]([NH:5][C:1](=[O:4])[CH:2]=[CH2:3])[CH:11]=2)[CH2:13][CH2:14]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131736989Tert-butyl (2-acrylamido-4-(4-(2-((tert-butoxycarbonyl)amino)ethyl)piperazin-1-yl)phenyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)carbamate

Product 1

HCID 118026128N-(5-(4-(2-aminoethyl)piperazin-1-yl)-2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamideYield 136.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl (2-acrylamido-4-(4-(2-((tert-butoxycarbonyl)amino)ethyl)piperazin-1-yl)phenyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)carbamate (17 g, 0.017 mmol) was stirred in DCM (1.0 ml), TFA (200 μl, 2.6 mmol) was added and the mixture was stirred at room temperature for 2 hours. Solvent was evaporated and remaining material was triturated with ether. The resulting solid was collected washed with ether and dried under stream of nitrogen to afford the title compound (15 mg, yield: 96%). 1H-NMR (400 MHz, MeOH-d4) δ 2.90 (br. s., 6H) 3.15-3.22 (m, 2H) 3.33-3.41 (m, 4H) 3.94 (s, 6H) 5.74-5.79 (m, 1H) 6.17 (s, 1H) 6.32-6.44 (m, 2H) 6.81 (s, 1H) 6.92-6.98 (m, 1H) 7.35 (d, 2H) 8.32 (d, 1H); ESI-MS: 644 [M+H]+.

Workup

  1. customSolvent was evaporated
  2. customwas triturated with ether
  3. customThe resulting solid was collected
  4. washwashed with ether
  5. customdried under stream of nitrogen

Sources & evidence

ORD record
ord-8e5ac32777e34cac9ba74bce36a3755e
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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