(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one → 8-fluoro-4-hydroxy-9-(((R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide

HRID 575481Notes

Reaction equation

HRID 575481 reaction equation
BrC1C(F)=CC2OCC(O)(C)C3SC(C(OCC)=O)=[N:11]C=3C=2C=1.C([C@]1(O)CCN(C)C1=O)#C.[F:34][C:35]1[C:36]([C:56]#[C:57][C@:58]2([OH:65])[CH2:62][CH2:61][N:60]([CH3:63])[C:59]2=[O:64])=[CH:37][C:38]2[C:44]3[N:45]=[C:46]([C:48]([O:50]CC)=O)[S:47][C:43]=3[C:42]([OH:54])([CH3:53])[CH2:41][O:40][C:39]=2[CH:55]=1>>[F:34][C:35]1[C:36]([C:56]#[C:57][C@:58]2([OH:65])[CH2:62][CH2:61][N:60]([CH3:63])[C:59]2=[O:64])=[CH:37][C:38]2[C:44]3[N:45]=[C:46]([C:48]([NH2:11])=[O:50])[S:47][C:43]=3[C:42]([OH:54])([CH3:53])[CH2:41][O:40][C:39]=2[CH:55]=1

Participants

4

Reactant 3

HCID 86693296(R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-oneHCID 86693414ethyl 9-bromo-8-fluoro-4-hydroxy-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylateHCID 86693416ethyl 8-fluoro-4-hydroxy-9-[2-[(3R)-3-hydroxy-1-methyl-2-oxo-pyrrolidin-3-yl]ethynyl]-4-methyl-5H-[1]benzoxepino[5,4-d]thiazole-2-carboxylate

Product 1

HCID 866935538-fluoro-4-hydroxy-9-(((R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxamide

Procedure

Similar to as described in General Procedure G, racemic ethyl 9-bromo-8-fluoro-4-hydroxy-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate was reacted with (R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one to give a diasteromeric mixture of ethyl 8-fluoro-4-hydroxy-9-(((R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)-4-methyl-4,5-dihydrobenzo[2,3]oxepino[4,5-d]thiazole-2-carboxylate. Following aminolysis of the ethyl ester (similar to as described in General Procedure M) a diasteromeric mixture of the titled compounds was obtained after purification by prep HPLC.

Workup

  1. customto give
  2. customwas obtained
  3. customafter purification by prep HPLC

Sources & evidence

ORD record
ord-cc948b9b440a465ea4df9ac8e6e8258c
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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