N-methyl-2-pyrrolidone → (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 1630328Notes

Reaction equation

HRID 1630328 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1I)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].CC[N:30]([CH:34]([CH3:36])C)[CH:31]([CH3:33])C.CN1C(=O)[CH2:41][CH2:40][CH2:39]1>>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1[N:30]1[CH2:31][CH2:33][C:40]([CH3:41])([CH3:39])[CH2:36][CH2:34]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 86691589HCID 86691589, compound

Product 1

HCID 71267856(S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylateYield 76%

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (300 mg, 0.613 mmol) and 4,4-dimethylpiperidine, HCl (138 mg, 0.920 mmol) in NMP (3 mL) was added DIEA (0.321 mL, 1.839 mmol) and the mixture was heated at 50° C. for 72 h. At this point LCMS indicated completion of reaction. Mixture was cooled to room temperature and purified by prep-HPLC to afford (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (220 mg, 0.464 mmol, 76% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.03 (s, 1H), 5.99 (s, 1H), 4.47 (q, J=7.1 Hz, 2H), 4.30-4.11 (m, 2H), 3.21-2.98 (m, 4H), 2.65 (s, 3H), 1.70-1.62 (m, 2H), 1.59-1.50 (m, 2H), 1.46 (t, J=7.1 Hz, 3H), 1.26 (s, 9H), 1.25-1.22 (m, 3H), 1.14 (s, 6H). LCMS (M+H)=475.2.

Workup

  1. customcompletion of reaction
  2. temperatureMixture was cooled to room temperature
  3. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-3004e6344ebe4741bbb0c15e035a33d4
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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