Sodium borohydride → 3-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-4-one

HRID 1021925Notes

Reaction equation

[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:5][C:4]([C:20]2[C:25]([CH:26]=[O:27])=[C:24]([N:28]3[C:40](=[O:41])[C:32]4=[CH:33][N:34]5[C:39]([CH2:38][CH2:37][CH2:36][CH2:35]5)=[C:31]4[CH:30]=[N:29]3)[N:23]=[CH:22][CH:21]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:27][CH2:26][C:25]1[C:24]([N:28]2[C:40](=[O:41])[C:32]3=[CH:33][N:34]4[C:39]([CH2:38][CH2:37][CH2:36][CH2:35]4)=[C:31]3[CH:30]=[N:29]2)=[N:23][CH:22]=[CH:21][C:20]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:19]=[C:13]3[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]3[N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of 202a (180 mg, 0.33 mmol) in methanol (25 mL) was added NaBH4 (37 mg, 0.99 mmol). The mixture was stirred at 20° C. for 2 h and quenched with water. It was then evaporated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 202 (120 mg, 66%) as a white solid. MS-ESI: [M+H]+ 554.3. 1H NMR (500 MHz, DMSO-d6) δ 8.53 (d, J=5.0 Hz, 1H), 8.25 (s, 1H), 8.19 (s, 1H), 8.07 (d, J=2.0 Hz, 1H), 7.61 (s, 1H), 7.45 (d, J=5.0 Hz, 1H), 7.43 (d, J=2.5 Hz, 1H), 5.89 (s, 1H), 4.65 (t, J=5.0 Hz, 1H), 4.34-4.32 (m, 2H), 4.26-4.20 (m, 2H), 3.93-3.91 (m, 2H), 3.58 (s, 3H), 3.49 (s, 2H), 3.06-3.04 (m, 2H), 2.79-2.77 (m, 2H), 2.35 (s, 3H), 2.04-1.96 (m, 2H), 1.93-1.86 (m, 2H).

Workup

customquenched with water
customIt was then evaporated under reduced pressure
customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record: ord-45147eb51f704180b521d8f7a25bd9df
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716274B2

Reaction notes

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