Sodium Hydroxide → 4-[2-((R)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-Phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid

HRID 240628Notes

Reaction equation

HRID 240628 reaction equation
C[O:2][C:3]([C:5]1[S:35][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[O:21][C@@H:22]3[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]3)[C:7]=2[C:6]=1[CH3:36])=[O:4].[OH-].[Na+]>CO.C1COCC1>[C:31]([O:30][C:28]([N:24]1[CH2:25][CH2:26][CH2:27][C@@H:22]([O:21][C:15]2[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=2[NH:13][C:12]2[C:7]3[C:6]([CH3:36])=[C:5]([C:3]([OH:4])=[O:2])[S:35][C:8]=3[N:9]=[CH:10][N:11]=2)[CH2:23]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 584131274-[2-((R)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

Product 1

HCID 584130574-[2-((R)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-Phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of 4-[2-((R)-1-tert-Butoxycarbonyl-piperidin-3-yloxy)-4-fluoro-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (1.65 g) in MeOH/THF (1:1; 20 ml) was treated with NaOH (2M; 8 ml) and heated at reflux for 10 mins. Organic solvent was removed in vacuo. HCl (2M; 8 ml) was added to pH 1 and water was added. The suspension was filtered and washed with water. The solid was suspended in EtOH and evaporated. The residue was triturated with Acetonitrile to give the desired product.

Workup

  1. temperatureheated
  2. temperatureat reflux for 10 mins
  3. customOrganic solvent was removed in vacuo
  4. additionHCl (2M; 8 ml) was added to pH 1 and water
  5. additionwas added
  6. filtrationThe suspension was filtered
  7. washwashed with water
  8. customevaporated
  9. customThe residue was triturated with Acetonitrile

Sources & evidence

ORD record
ord-0cce96f0b7684110914f88a568983c6f
Source dataset
uspto-grants-2014_02
Patent number
US08648068B2

Reaction notes

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