Diisobutylaluminumhydride → 3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60154Notes

Reaction equation

[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:28]=[CH:27][C:13]2[N:14]([CH3:26])[C:15](=[O:25])[N:16]([CH2:19][CH2:20][C:21](OC)=[O:22])[C:17](=[O:18])[C:12]=2[CH:11]=1)([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C>C1COCC1>[OH:22][CH2:21][CH2:20][CH2:19][N:16]1[C:17](=[O:18])[C:12]2[CH:11]=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:1]([CH3:3])[CH3:2])[N:28]=[CH:27][C:13]=2[N:14]([CH3:26])[C:15]1=[O:25]

Participants

Conditions

Temperature: -55 °C

Procedure

To a solution of methyl 3-(6-(2-isopropylphenyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[3,4-d]pyrimidin-3(4H)-yl)propanoate (140 mg, 0.367 mmol) in THF (3.7 mL) at −55° C. was added diisobutylaluminium hydride (1.1 mL, 1.58 mmol, 1.5M in toluene) dropwise. The reaction was stirred at −55° C. for 1 h, warmed to 0° C., quenched with aq. NH4Cl (10 mL) and diluted with EA (20 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated to give 3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (20 mg, 15% yield) as a white solid. 1H NMR (DMSO-d6) δ: 8.99 (s, 1H), 7.85 (s, 1H), 7.49-7.43 (m, 2H), 7.29-7.28 (m, 2H), 4.51-4.49 (m, 1H), 4.03-4.00 (m, 2H), 3.633 (s, 3H), 3.49-3.45 (m, 2H), 3.17-3.14 (m, 1H), 1.77-1.73 (m, 1H), 1.15-1.14 (m, 6H). LCMS: MH+ 354 and TR=2.246 min.

Workup

temperaturewarmed to 0° C.
customquenched with aq. NH4Cl (10 mL)
additiondiluted with EA (20 mL)
washThe organic layer was washed with brine (10 mL)
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-3bab7b1576084080aa3e26dc6e6dec14
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440973B2

Reaction notes

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