Hydrochloric Acid → Rac-n2-[4-(4-amino-1-tetrahydro-1h-3-pyrrolyl-1h-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl]-5,7-dimethyl-1,3-benzoxazol-2-amine

HRID 897945Notes

Reaction equation

HRID 897945 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:30]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31]3)[N:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19]4[O:20][C:21]5[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][C:22]=5[N:23]=4)=[CH:14][CH:13]=3)[C:4]=12>CC(C)=O>[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:30]3[CH2:34][CH2:33][NH:32][CH2:31]3)[N:10]=[C:11]([C:12]3[CH:13]=[CH:14][C:15]([NH:18][C:19]4[O:20][C:21]5[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][C:22]=5[N:23]=4)=[CH:16][CH:17]=3)[C:4]=12

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22346993HCID 22346993, compound

Product 1

HCID 69778871Rac-n2-[4-(4-amino-1-tetrahydro-1h-3-pyrrolyl-1h-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl]-5,7-dimethyl-1,3-benzoxazol-2-amineYield 35%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
45 °C

Procedure

6 N Hydrochloric acid (10 mL) was added to a solution of rac-tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-pyrrolidinecarboxylate (1.029 g) in acetone (10 mL) and the reaction mixture was stirred at 45° C. for 5 h. The reaction mixture was filtered, and the resulting opaque filtrate was concentrated to afford an orange solid. Purification by preparative RP-HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 20 min at 21 mL/min using a 8 μm Hypersil HS C18, 250×21 mm column, tr=6.2-7.5 min) afforded rac-N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl]-5,7-dimethyl-1,3-benzoxazol-2-amine as an off-white solid (0.148 g, 35%). 1H NMR (DMSO-d6, 400 MHz) 2.15-2.22 (m, 2H), 2.40 (s, 3H), 2.50 (s, 3H), 2.93-4.04 (m, 5H), 5.31 (m, 1H), 6.79 (s, 1H), 7.11 (s, 1H), 7.66 (d, 2H), 7.93 (d, 2H), 8.24 (s, 1H), 10.85 (s, 1H); RP-HPLC Rt 10.603 min, 99% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); m/z 441 (MH+).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe resulting opaque filtrate was concentrated
  3. customto afford an orange solid
  4. customPurification by preparative RP-HPLC (25 to 100% CH3CN in 0.1 N aqueous ammonium acetate over 20 min at 21 mL/min
  5. customa 8 μm Hypersil HS C18, 250×21 mm column, tr=6.2-7.5 min

Sources & evidence

ORD record
ord-7cc494eabfde45ebb92fb897161c0fb8
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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