Dimethylformamide → Acetic acid 2-(3-{(R)-(4-carbamimidoylphenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester acetic acid salt

HRID 2089699Notes

Reaction equation

HRID 2089699 reaction equation
[NH2:1][C:2](=[N:49]C(OCC(C)=C)=O)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@@H:10]([C:27]2[N:31]=[C:30]([O:32][CH2:33][O:34][C:35]([O:37][CH:38]([CH2:41][CH3:42])[CH2:39][CH3:40])=[O:36])[N:29]([C:43]3[N:48]=[CH:47][CH:46]=[CH:45][N:44]=3)[N:28]=2)[C:11]2[C:12]([F:26])=[C:13]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=2)[O:14][CH2:15][CH2:16][O:17][C:18](=[O:20])[CH3:19])=[CH:5][CH:4]=1.CN(C=O)C>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)(=O)C>[C:18]([OH:20])(=[O:17])[CH3:19].[C:2]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C@@H:10]([C:27]2[N:31]=[C:30]([O:32][CH2:33][O:34][C:35]([O:37][CH:38]([CH2:39][CH3:40])[CH2:41][CH3:42])=[O:36])[N:29]([C:43]3[N:44]=[CH:45][CH:46]=[CH:47][N:48]=3)[N:28]=2)[C:11]2[C:12]([F:26])=[C:13]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=2)[O:14][CH2:15][CH2:16][O:17][C:18](=[O:20])[CH3:19])=[CH:7][CH:8]=1)(=[NH:1])[NH2:49]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86677416Acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester

Product 1

HCID 86677418Acetic acid 2-(3-{(R)-(4-carbamimidoylphenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester acetic acid salt

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester (Example 51, 266 mg), DMF (2 mL) and acetic acid (0.196 mL), tetrakis(triphenylphosphine) palladium (0) (20 mg) was added, and the resulting mixture was stirred overnight at an external temperature of 45° C. After cooling the mixture to room temperature, the reaction solution containing the captioned compound was divided into 4 equal lots, and used for the following reactions.

Workup

  1. additionwas added
  2. temperatureAfter cooling the mixture to room temperature
  3. additionthe reaction solution containing the captioned compound

Sources & evidence

ORD record
ord-81ff6cccbf6a45a8bd5a02aea271b8e8
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

Loading…