Water → (S)-1-((S)-2-((S)-2-acrylamidopropanamido)-3,3-dimethylbutanoyl)-N-(4-(3-chloro-2,4-difluorophenylamino)-7-methoxyquinazolin-6-yl)pyrrolidine-2-carboxamide hydrochloride

HRID 75708Notes

Reaction equation

HRID 75708 reaction equation
Cl.[NH2:2][C@@H:3]([CH3:44])[C:4]([NH:6][C@@H:7]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[C:15]([NH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]2[NH:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[C:33]([Cl:38])[C:32]=1[F:39])=[O:16])=[O:9])=[O:5].C([O-])(O)=O.[Na+].O.[C:51](Cl)(=[O:54])[CH:52]=[CH2:53]>C1COCC1>[ClH:38].[C:51]([NH:2][C@@H:3]([CH3:44])[C:4]([NH:6][C@@H:7]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[C:15]([NH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[N:24]=[CH:23][N:22]=[C:21]2[NH:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[C:33]([Cl:38])[C:32]=1[F:39])=[O:16])=[O:9])=[O:5])(=[O:54])[CH:52]=[CH2:53]

Participants

6

Reactant 4

HCID 962WaterHCID 13140Acryloyl chlorideHCID 516892Sodium Bicarbonate2×HCID 86688404(S)-1-((S)-2-((S)-2-aminopropanamido)-3,3-dimethylbutanoyl)-N-(4-(3-chloro-2,4-difluorophenylamino)-7-methoxyquinazolin-6-yl)pyrrolidine-2-carboxamide hydrochloride

Product 1

HCID 86688403(S)-1-((S)-2-((S)-2-acrylamidopropanamido)-3,3-dimethylbutanoyl)-N-(4-(3-chloro-2,4-difluorophenylamino)-7-methoxyquinazolin-6-yl)pyrrolidine-2-carboxamide hydrochlorideYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The compound (30 mg, 0.046 mmol) obtained in Example 12 and NaHCO3 (11.6 mg, 0.14 mmol) were dissolved in THF (0.8 mL): H2O (0.2 mL), and acryloyl chloride (0.004 mL, 0.046 mmol) was added thereto at 0° C. The mixture was stirred at 0° C. for 30 min, and an aqueous solution of NaHCO3 was added thereto, followed by washing several times with chloroform. The organic layer was dried over sodium sulfate, filtered and distilled under reduced pressure, and purified by column chromatography to obtain the title compound (15 mg, 8%).

Workup

  1. customat 0° C
  2. washby washing several times with chloroform
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. distillationdistilled under reduced pressure
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-f2dff88f1c8b4db09d869ade374c63c4
Source dataset
uspto-grants-2014_09
Patent number
US08835458B2

Reaction notes

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