Hydrochloric Acid → [2-(4-Azetidin-3-yl-2,6-dichlorophenyl)thiazolo[5,4-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

HRID 2366253Notes

Reaction equation

HRID 2366253 reaction equation
Cl.C(OC([N:9]1[CH2:12][CH:11]([C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([C:20]3[S:21][C:22]4[C:23]([NH:29][C:30]5[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32][N:31]=5)=[N:24][CH:25]=[CH:26][C:27]=4[N:28]=3)=[C:15]([Cl:37])[CH:14]=2)[CH2:10]1)=O)(C)(C)C>>[NH:9]1[CH2:10][CH:11]([C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([C:20]3[S:21][C:22]4[C:23]([NH:29][C:30]5[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32][N:31]=5)=[N:24][CH:25]=[CH:26][C:27]=4[N:28]=3)=[C:15]([Cl:37])[CH:14]=2)[CH2:12]1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 668016723-{3,5-Dichloro-4-[4-(6-methylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-phenyl}-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 56952515[2-(4-Azetidin-3-yl-2,6-dichlorophenyl)thiazolo[5,4-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amineYield 40%

Conditions

Temperature
40 °C

Procedure

HCl (4N in dioxane, 5 mL) was added to 3-{3,5-dichloro-4-[4-(6-methylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-phenyl}-azetidine-1-carboxylic acid tert-butyl ester (0.062 g, 0.114 mmol). The suspension was heated at 40° C. for 1 hour and then cooled to room temperature. The volatiles were removed under reduced pressure and the resultant residue was triturated with a mixture of EtOAc/DCM and then purified by column chromatography on silica gel eluting with 0-5% 2N NH3/MeOH in DCM to afford the title compound as an off-white solid (20 mg, 40% yield). 1H NMR (400 MHz, CDCl3): δ 8.65 (d, J=1.2 Hz, 1H), 8.46 (d, J=5.6 Hz, 1H), 7.84 (d, J=5.6 Hz, 1H), 7.75 (s, 2H), 7.63 (s, 1H), 3.99-3.90 (m, 1H), 3.85 (t, J=7.6 Hz, 2H), 3.61 (t, J=6.9 Hz, 2H), 2.41 (s, 3H). LCMS (Method C): RT=2.21 min, m/z: 443 [M+H+].

Workup

  1. temperaturecooled to room temperature
  2. customThe volatiles were removed under reduced pressure
  3. customthe resultant residue was triturated with a mixture of EtOAc/DCM
  4. custompurified by column chromatography on silica gel eluting with 0-5% 2N NH3/MeOH in DCM

Sources & evidence

ORD record
ord-a82d626047f94da39e684856daf67392
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

Loading…