Triethylamine → Ethyl 2-aminopyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1466601Notes

Reaction equation

[NH2:1][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:5]([NH2:12])[NH:4][N:3]=1.CO[CH:15](OC)[CH2:16][CH:17](OC)OC.C(N(CC)CC)C>CN(C=O)C>[NH3:1].[NH2:12][C:5]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]2[N:1]=[CH:15][CH:16]=[CH:17][N:3]2[N:4]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of ethyl 3,5-diamino-1H-pyrazole-4-carboxylate (1.0 g, 5.9 mmol), 1,1,3,3-tetramethoxypropane (2.9 mL, 18 mmol), triethylamine (2 mL, 10 mmol), and DMF (15 mL) was heated at 100° C. for 14 hrs, then a further 2 mL of 1,1,3,3-tetramethoxypropane was added. After adding the additional 1,1,3,3-tetramethoxypropane, a significant by-product was noted and heating was stopped immediately. The reaction was cooled to room temperature and the DMF was removed in vacuo. The residue was partitioned between DCM and water, then the organic layer was concentrated and the residue purified by silica chromatography, eluting with 95:5 DCM: 2M methanolic ammonia solution to afford 420 mg (35%) of ethyl 2-aminopyrazolo[1,5-a]pyrimidine-3-carboxylate. 1H NMR (500 MHz, CDCl3) δ 8.57 (dd, J=4.3, 1.6, 1H), 8.43 (dd, J=6.7, 1.6, 1H), 6.84 (dd, J=6.7, 4.4, 1H), 5.52 (s, 2H), 4.48 (q, J=7.1, 2H), 1.45 (t, J=7.1, 3H).

Workup

temperatureheating
temperatureThe reaction was cooled to room temperature
customthe DMF was removed in vacuo
customThe residue was partitioned between DCM and water
concentrationthe organic layer was concentrated
customthe residue purified by silica chromatography
washeluting with 95:5 DCM

Sources & evidence

ORD record: ord-8d7baaaf473446268d0b7f7776476a57
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999998B2

Reaction notes

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