Hydrochloric Acid → HCID 178424096, compound

HRID 898037Notes

Reaction equation

HRID 898037 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:29]3[CH2:34][CH2:33][C@H:32]([C:35]([O:37]CC)=[O:36])[CH2:31][CH2:30]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]4[O:19][C:20]5[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:21]=5[N:22]=4)=[CH:13][CH:12]=3)[C:3]=12.[OH-].[Na+].Cl>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:29]3[CH2:34][CH2:33][C@H:32]([C:35]([OH:37])=[O:36])[CH2:31][CH2:30]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]4[O:19][C:20]5[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:21]=5[N:22]=4)=[CH:13][CH:12]=3)[C:3]=12

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178472395HCID 178472395, compound

Product 1

HCID 178424096HCID 178424096, compoundYield 27.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

cis-Ethyl 4-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-cyclohexanecarboxylate (0.10 g, 0.19 mmol), aqueous sodium hydroxide (1 M, 2 mL, 2 mmol), and methanol (2 mL) were combined and heated under an air condenser at 70° C. for 14 h. The residue was acidified with aqueous hydrochloric acid (3 M, 2 mL, 6 mmol), and extracted with 10% methanol/dichloromethane (3×20 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated. Purification of the product by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8μ Hypersil HS C18, 250×21 mm column, Rt 8.8-10.9 min) afforded cis-4-(4-Amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-cyclohexanecarboxylic acid as a cream-colored powder (0.026 g, 0.052 mmol); RP-HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a 5μ Hypersil HS C18, 250×4.6 mm column) Rt 9.03 min; MS (MH)+ 498.

Workup

  1. extractionextracted with 10% methanol/dichloromethane (3×20 mL)
  2. dry with materialThe combined organic fractions were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the product by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

Sources & evidence

ORD record
ord-7fc2ece4f78e4ed484e36b43401cd345
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

Loading…