Lithium hydroxide, monohydrate → HCID 66551542, compound

HRID 1410005Notes

Reaction equation

HRID 1410005 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:38]=[CH:37][S:36][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[CH:28][CH:27]=4)=[O:25])[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:38]=[CH:37][S:36][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([NH:23][C:24]([C:26]4[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=4)=[O:25])[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 68379395HCID 68379395, compound

Product 1

HCID 66551542HCID 66551542, compoundYield 64.8%

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)pyrrolidin-3-ylcarbamoyl)benzoate (190 mg, 0.255 mmol) and LiOH.H2O (149 mg, 3.55 mmol) in 2 mL of water, 10 mL of methanol and 15 mL of THF was stirred at room temperature for 2 hours. The solvent was evaporated after the solution was acidified by 2N HCl to pH=2 and the residue was dissolved in 50 mL of THF, filtered to remove the salts. The filtrate was evaporated and the residue was 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: 25% acetonitrile/75% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% 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)pyrrolidin-3-ylcarbamoyl)benzoic acid (86 mg, 46.5%) as a solid. 1H NMR (300 MHz, DMSO): δ 9.63 (s, 1H), 8.36-8.79 (m, 2H), 8.02-7.88 (m, 5H), 7.60-7.50 (m, 1H), 6.93 (d, 1H, J=8.7 Hz), 4.61-4.59 (m, 1H), 3.95-3.66 (m, 10H), 2.28-2.10 (m, 2H). LC-MS: 521 [M+H]+; 518.8 [M−H]−, tR=1.36 min. HPLC: 99.85% at 214 nm, 99.84% at 254 nm, tR=4.67 min.

Workup

  1. customThe solvent was evaporated after the solution
  2. dissolutionthe residue was dissolved in 50 mL of THF
  3. filtrationfiltered
  4. customto remove the salts
  5. customThe filtrate was evaporated
  6. customthe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-71a06e2e93324c4a94ec8acc20a59be3
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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