Hydrochloric Acid → 4-(1-(7-(5,6-Dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid

HRID 1410102Notes

Reaction equation

HRID 1410102 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([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)=[N:7][C:8]=1[O:9][CH3:10].O[Li].O.Cl>CO.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([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)=[N:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 68379246Methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate

Product 1

HCID 665501184-(1-(7-(5,6-Dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acidYield 20.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate (350 mg, 0.65 mmol) in 20 mL of methanol and 40 mL of THF was added a solution of LiOH.H2O (274 mg, 6.5 mmol) in one portion at room temperature. Then the solution was stirred at room temperature for 24 hours. The solution was acidified with 1N HCl to pH=4. The solvent 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: 30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(5,6-dimethoxypyridin-2-ylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid (70 mg, 20.5%) as a pale yellow solid. 1H NMR (300 MHz, DMSO): δ 8.87-8.18 (m, 2H), 8.67 (s, 1H), 8.03-7.96 (m, 5H), 7.44 (d, 1H, J=8.7 Hz), 4.66 (brs, 1H), 4.11 (brs, 2H), 3.90 (s, 3H), 3.78 (s, 3H), 3.68 (brs, 2H), 2.27 (brs, 1H), 2.08 (brs, 1H). LC-MS: 522 [M+H]+, tR=1.44 min. HPLC: 99.68% at 214 nm, 99.31% at 254 nm, tR=6.98 min.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  3. wait30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-1daa59b62a3b403ea3587cf4bfeaa086
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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