N-methyl-2-pyrrolidone → HCID 67064708, compound

HRID 1409183Notes

Reaction equation

HRID 1409183 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH:11]3[CH2:13][CH2:12]3)[CH:10]=[C:6]2[N:5]=[C:4]([NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][C:19]([C:22]([OH:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=2)[CH:3]=1.[OH:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CN1C(=O)CCC1>CN(C=O)C>[CH:11]1([C:9]2[CH:10]=[C:6]3[N:5]=[C:4]([NH:14][C:15](=[O:26])[C:16]4[CH:21]=[CH:20][C:19]([C:22]([OH:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=4)[CH:3]=[C:2]([N:31]4[CH2:32][CH2:33][CH:28]([OH:27])[CH2:29][CH2:30]4)[N:7]3[N:8]=2)[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 79341Piperidin-4-olHCID 86652274HCID 86652274, compound

Product 1

HCID 67064708HCID 67064708, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 2 mL microwave vial was placed N-(7-chloro-2-cyclopropylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2J, 100 mg, 0.27 mmol) and 4-hydroxypiperidine (55.0 mg, 0.54 mmol). To the sealed vial was then added NMP (2 ml) and the mixture was then heated in the microwave at 120° C. for 15 minutes. After cooling to room temperature, DMF (1 ml) was added. The crude product mixture was filtered by syringe filter and purified by preparatory HPLC (20-40% ACN/water, TFA mode). Lyophilization of the collected fractions gave the titled compound product (30 mg, 26% yield) as an off-white powder. 1H NMR (400 MHz, DMSO-d6) δ=10.78 (s, 1H), 7.98 (d, J=8.6 Hz, 2H), 7.59 (d, J=8.6 Hz, 2H), 7.34 (s, 1H), 6.02 (s, 1H), 5.18 (s, 1H), 4.84 (d, J=4.3 Hz, 1H), 4.12 (d, J=12.6 Hz, 2H), 3.79 (dd, J=4.2, 8.5 Hz, 1H), 3.41-3.36 (m, 1H), 2.11-2.00 (m, 1H), 1.91 (br. s., 2H), 1.65-1.51 (m, 2H), 1.45 (s, 6H), 1.04-0.94 (m, 2H), 0.88-0.75 (m, 2H); ESI-MS: m/z 436.3 (M+H)+.

Workup

  1. filtrationThe crude product mixture was filtered by syringe
  2. filtrationfilter
  3. custompurified by preparatory HPLC (20-40% ACN/water, TFA mode)

Sources & evidence

ORD record
ord-ea4c4df788a7429fbe6eb0559dc940fb
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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