Glutathione → (S)-2-amino-5-((R)-1-(carboxymethylamino)-3-(3-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenylamino)-3-oxopropylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid

HRID 2276820Notes

Reaction equation

HRID 2276820 reaction equation
[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23]([NH:27][C:28](=[O:31])[CH:29]=[CH2:30])[CH:24]=[CH:25][CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[NH2:32][C@@H:33]([CH2:37][CH2:38][C:39]([NH:41][C@H:42]([C:45]([NH:47][CH2:48][C:49]([OH:51])=[O:50])=[O:46])[CH2:43][SH:44])=[O:40])[C:34]([OH:36])=[O:35]>C(Cl)Cl.CO>[NH2:32][C@@H:33]([CH2:37][CH2:38][C:39]([NH:41][C@@H:42]([CH2:43][S:44][CH2:30][CH2:29][C:28]([NH:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([NH:20][C:3]2[C:2]([F:1])=[CH:7][N:6]=[C:5]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=3)[N:4]=2)[CH:22]=1)=[O:31])[C:45]([NH:47][CH2:48][C:49]([OH:51])=[O:50])=[O:46])=[O:40])[C:34]([OH:36])=[O:35]

Participants

5

Reactant 2

HCID 124886GlutathioneHCID 59174488Spebrutinib

Product 1

HCID 89908213(S)-2-amino-5-((R)-1-(carboxymethylamino)-3-(3-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenylamino)-3-oxopropylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acidYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-(3-{5-fluoro-2-[4-(2-methoxy-ethoxy)-phenylamino]-pyrimidin-4-ylamino}-phenyl)-acrylamide 3 (0.1 g, 0.236 mmol) and glutathione (0.1 g, 0.325 mmol) in DCM (10 mL) and CH3OH (10 mL) was added TEA (0.1 g, 0.988 mmol) dropwise at 0° C. The resulting mixture was stirred at room temperature for 16 h and then concentrated. The residue was washed with H2O and dried to afford the title compound, (S)-2-amino-5-((R)-1-(carboxymethylamino)-3-(3-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenylamino)-3-oxopropylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid (0.17 g, 100%).

Workup

  1. concentrationconcentrated
  2. washThe residue was washed with H2O
  3. customdried

Sources & evidence

ORD record
ord-c10962dc54cb4eb3a4962baf59455781
Source dataset
uspto-grants-2015_09
Patent number
US09133134B2

Reaction notes

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