Water → (2-Acryloylamino-4-morpholin-4-yl-phenyl)-{6-[3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-ureido]-pyrimidin-4-yl}-carbamic acid tert-butyl ester

HRID 58157Notes

Reaction equation

HRID 58157 reaction equation
[C:1]([O:5][C:6](=[O:52])[N:7]([C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[CH:41][C:40]=1[NH2:51])[C:8]1[CH:13]=[C:12]([N:14]([CH3:38])[C:15]([N:17]([C:26]2[C:31]([Cl:32])=[C:30]([O:33][CH3:34])[CH:29]=[C:28]([O:35][CH3:36])[C:27]=2[Cl:37])[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[O:16])[N:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[C:53](Cl)(=[O:56])[CH:54]=[CH2:55].O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:52])[N:7]([C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH2:46][CH2:47][O:48][CH2:49][CH2:50]2)=[CH:41][C:40]=1[NH:51][C:53](=[O:56])[CH:54]=[CH2:55])[C:8]1[CH:13]=[C:12]([N:14]([CH3:38])[C:15]([N:17]([C:26]2[C:27]([Cl:37])=[C:28]([O:35][CH3:36])[CH:29]=[C:30]([O:33][CH3:34])[C:31]=2[Cl:32])[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:23])([CH3:24])[CH3:25])=[O:16])[N:11]=[CH:10][N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 13140Acryloyl chlorideHCID 131736976HCID 131736976, compound

Product 1

HCID 131736977(2-Acryloylamino-4-morpholin-4-yl-phenyl)-{6-[3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-ureido]-pyrimidin-4-yl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-amino-4-morpholin-4-yl-phenyl)-{6-[3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-ureido]-pyrimidin-4-yl}-carbamic acid tert-butyl ester (80 g, 0.103 mmol) in DCM (5 mL) was added a solution of TEA (10 mg/mL, 1.2 mL, 0.12 mmol) and a solution of acryloyl chloride (10 mg/mL, 1 mL, 0.11 mmol) dropwise at 0° C., and the resulting mixture was stirred at room temperature for 1 hour. LC-MS showed that the reaction was complete. Water (5 mL) was added to quench the reaction, and the reaction mixture was extracted with DCM. The combined extracts were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under vacuum to give crude product, which was used for the next step without further purification.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with DCM
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe filtrate was evaporated under vacuum
  8. customto give crude product, which
  9. customwas used for the next step without further purification

Sources & evidence

ORD record
ord-961a3ea8905f4989952aa32d70f701f3
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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