Sodium → N-(7-butoxypyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1409221Notes

Reaction equation

HRID 1409221 reaction equation
[Na].Cl[C:3]1[N:8]2[N:9]=[CH:10][CH:11]=[C:7]2[N:6]=[C:5]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:4]=1.[O-:25][CH2:26][CH2:27][CH2:28][CH3:29].[Na+]>C(O)CCC>[CH2:26]([O:25][C:3]1[N:8]2[N:9]=[CH:10][CH:11]=[C:7]2[N:6]=[C:5]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:4]=1)[CH2:27][CH2:28][CH3:29]

Participants

5

Reactant 3

HCID 5360545SodiumHCID 23669364Sodium n-butylateHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 58207324N-(7-butoxypyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent2×

Procedure

Sodium metal was added to dry butanol (5 mL, 54.6 mmol) at 0° C. then the reaction was raised to room temperature. Then, the next day, a solid precipitated. Stir N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (100 mg, 0.302 mmol) in dry butanol (5 mL). Add the previously made sodium butoxide (58 mg, 0.605 mmol) at 0° C. then raise to room temperature. After stirring overnight, the majority of the reaction was converted to product. Deamination was observed where the amide bond of the compound was cleaved. The compound was filtered and purified by preparatory HPLC 40-50% (MeCN/H2O gradient+0.01% TFA). Received 29.1 mg of a white solid (26%). 1H NMR (DMSO-d6) δ: 11.08 (s, 2H), 8.09 (d, J=2.3 Hz, 2H), 8.01 (d, J=8.6 Hz, 4H), 7.61 (d, J=8.6 Hz, 4H), 7.54 (s, 2H), 6.40 (d, J=2.0 Hz, 2H), 5.19 (s, 2H), 4.46 (t, J=6.4 Hz, 4H), 1.79-1.98 (m, 4H), 1.49-1.62 (m, 4H), 1.46 (s, 12H), 0.99 (t, J=7.5 Hz, 3H). ESI-MS: m/z 369.4 (M+H)+.

Workup

  1. customThen, the next day, a solid precipitated
  2. temperaturethen raise to room temperature
  3. filtrationThe compound was filtered
  4. custompurified by preparatory HPLC 40-50% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-644f57164a214bae89f10386222a3f7b
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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