Lithium hydroxide, monohydrate → HCID 66551543, compound

HRID 1410007Notes

Reaction equation

HRID 1410007 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([NH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=4)=[O:26])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O[Li].O>O.CO.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:39]=[CH:38][S:37][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([NH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=4)=[O:26])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68379114HCID 68379114, compound

Product 1

HCID 66551543HCID 66551543, compoundYield 18.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoate (250 mg, 0.45 mmol) and LiOH.H2O (191 mg, 4.5 mmol) in 2 mL of water, 12 mL of methanol and 30 mL of THF was stirred at room temperature for 1 hour. The solvent was evaporated and the residue was suspended in 30 mL of THF, then treated with 2N HCl to pH=2. The solvent was evaporated and the residue was dissolved in 50 mL of THF, filtered to remove the salts. The filtrate was evaporated and crude purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 28% acetonitrile/72% water (0.1% TFA V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoic acid (45 mg, 18.4%) as a solid. 1H NMR (300 MHz, DMSO): δ 13.20 (brs, 1H), 9.63 (s, 1H), 8.85 (s, 1H), 8.04-7.95 (m, 4H), 7.63 (s, 1H), 7.41-7.32 (m, 2H), 6.88-6.85 (m, 1H), 5.34-5.31 (m, 1H), 4.71-4.52 (m, 2H), 3.70 (s, 3H), 3.67 (s, 3H), 3.04-2.97 (m, 2H), 2.04-1.96 (m, 4H). LC-MS: 535 [M+H]+; 532.9 [M−H]−, tR=1.43 min. HPLC: 99.26% at 214 nm, 99.79% at 254 nm, tR=5.37 min.

Workup

  1. customThe solvent was evaporated
  2. additiontreated with 2N HCl to pH=2
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in 50 mL of THF
  5. filtrationfiltered
  6. customto remove the salts
  7. customThe filtrate was evaporated
  8. customcrude purified by preparative HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-029dc1b984a0410dac927de0b6283394
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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