1-Ethyl 4-methyl 2-acetylsuccinate → HCID 178499488, compound

HRID 472871Notes

Reaction equation

[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][C:2]=1[C:11]1[CH:15]=[C:14]([NH2:16])[NH:13][N:12]=1.[C:17]([CH:20]([CH2:26][C:27]([O:29][CH3:30])=[O:28])[C:21](OCC)=[O:22])(=O)[CH3:18]>CC1C=CC=CC=1C.S(O)(C1C=CC(C)=CC=1)(=O)=O.O>[OH:22][C:21]1[N:13]2[N:12]=[C:11]([C:2]3[CH:3]=[CH:4][C:5]4[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=4[CH:1]=3)[CH:15]=[C:14]2[N:16]=[C:17]([CH3:18])[C:20]=1[CH2:26][C:27]([O:29][CH3:30])=[O:28]

Participants

Conditions

Temperature: 150 °C

Procedure

A suspension of 3-(5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazol-5-amine (6 g, 28.1 mmol), 1-ethyl 4-methyl 2-acetylsuccinate (24.52 mL, 141 mmol) and Ts-OH.H2O (0.096 g, 0.506 mmol) in o-xylene (200 mL) was heated at 150° C. (oil bath temp) for 16 h. (Note: Mixture became homogeneous and in about 15 min slowly yellow solid started crashing out of the reaction.). Then, the reaction mixture was cooled, diluted with hexanes (300 mL), filtered, washed with hexanes and dried to afford methyl 2-(7-hydroxy-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (8.4 g, 23.90 mmol, 85% yield) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 12.35 (s, 1H), 7.78-7.62 (m, 2H), 7.15 (d, J=8.5 Hz, 1H), 6.52 (s, 1H), 3.64 (s, 3H), 3.58 (s, 2H), 2.82-2.77 (m, 4H), 2.33 (s, 3H), 1.78 (t, J=3.0 Hz, 4H). LCMS (M+H)=352.3.

Workup

customslowly yellow solid started crashing out of the reaction
temperatureThen, the reaction mixture was cooled
filtrationfiltered
washwashed with hexanes
customdried

Sources & evidence

ORD record: ord-2196f8b476b944e4b023495de872d293
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633200B2

Reaction notes

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