tert-butyl N-(2-oxoethyl)carbamate → Tert-butyl (2-(4-(3-acrylamido-4-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)piperazin-1-yl)ethyl)carbamate

HRID 58209

Reaction equation

HRID 58209 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([Cl:19])[C:10]=1[NH:20][C:21](=[O:48])[N:22]([C:24]1[N:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([N:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[CH:33][C:32]=2[NH:43][C:44](=[O:47])[CH:45]=[CH2:46])[CH:25]=1)[CH3:23].[C:49]([O:53][C:54](=[O:59])[NH:55][CH2:56][CH:57]=O)([CH3:52])([CH3:51])[CH3:50].C([BH3-])#N.[Na+]>C1COCC1.CO>[C:44]([NH:43][C:32]1[CH:33]=[C:34]([N:37]2[CH2:38][CH2:39][N:40]([CH2:57][CH2:56][NH:55][C:54](=[O:59])[O:53][C:49]([CH3:52])([CH3:51])[CH3:50])[CH2:41][CH2:42]2)[CH:35]=[CH:36][C:31]=1[NH:30][C:26]1[CH:25]=[C:24]([N:22]([CH3:23])[C:21]([NH:20][C:10]2[C:9]([Cl:8])=[C:14]([O:15][CH3:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=2[Cl:19])=[O:48])[N:29]=[CH:28][N:27]=1)(=[O:47])[CH:45]=[CH2:46]

Participants

6

Reactant 3

HCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5003444Sodium cyanoborohydrideHCID 121317870N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamide 2,2,2-trifluoroacetate

Product 1

HCID 118034209Tert-butyl (2-(4-(3-acrylamido-4-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)piperazin-1-yl)ethyl)carbamateYield 54.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamide 2,2,2-trifluoroacetate (Procedure 2L, Example 157) (30 g, 0.042 mmol) in THF (1.0 ml) and MeOH (1.0 ml) was added tert-butyl(2-oxoethyl)carbamate (13 g, 0.08 mmol). The reaction mixture was stirred at room temperature for 10 minutes. Sodium cyanoborohydride (7.0 g, 0.12 mmol) was added and the reaction mixture was stirred at room temperature over night. Solvent was evaporated and saturated NaHCO3 solution was added. The mixture was extracted three times with DCM. Combined organic layer was dried over Na2SO4 and evaporated. The remaining material was purified by flash chromatography on silica eluting with 0% to 15% MeOH in DCM to afford the title compound (17 mg, yield: 54%) ESI-MS: 744 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature over night
  2. customSolvent was evaporated
  3. additionsaturated NaHCO3 solution was added
  4. extractionThe mixture was extracted three times with DCM
  5. dry with materialCombined organic layer was dried over Na2SO4
  6. customevaporated
  7. customThe remaining material was purified by flash chromatography on silica eluting with 0% to 15% MeOH in DCM

Sources & evidence

ORD record
ord-4a2ae5a91c584f4a99a33db22fef9b1a
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Linked notes

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