Sodium hydride → 5-chloro-4-(6-iodo-1H-indazol-1-yl)pyrimidin-2-amine

HRID 1398479Notes

Reaction equation

[I:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:14]1[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([NH2:21])[N:15]=1>CN(C=O)C>[Cl:20][C:19]1[C:14]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=3)[CH:6]=[N:7]2)=[N:15][C:16]([NH2:21])=[N:17][CH:18]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 6-iodo-1H-indazole (100 mg, 0.41 mmol) in DMF (3 mL) was added NaH (60% oil dispersion, 32 mg, 0.82 mmol) at 0° C. The mixture was stirred at 0° C. to RT for 10 min before addition of 4,5-dichloropyrimidin-2-amine (134.4 mg, 0.82 mmol). The mixture was stirred at 50° C. for 2 hr, then quenched with water and extracted with DCM (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. LC-MS (Method B) indicated a mixture of title compound [67%, Retention time=2.11 min, m/z=+371.9/373.9 (M+H)+] and an isomeric by-product [10%, Retention time=2.07 min, m/z=+371.9/373.9 (M+H)+]. Purification by flash chromatography (Isolute column, 50% EtOAc in heptane) afforded the title compound: 1H NMR (500 MHz, DMSO) δ 7.31 (2H, br. s.), 7.65 (1H, dd, J=8.51, 1.26 Hz), 7.71 (1H, d, J=8.20 Hz), 8.45-8.48 (1H, m), 8.56-8.71 (1H, m), 8.61 (1H, s); LC-MS: m/z=+371.9 (M+H)+.

Workup

customquenched with water
extractionextracted with DCM (2×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
additiona mixture of title compound [67%, Retention time=2.11 min, m/z=+371.9/373.9 (M+H)+]
customPurification by flash chromatography (Isolute column, 50% EtOAc in heptane)

Sources & evidence

ORD record: ord-ff24daf594fb4d20aa47807a973c6201
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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