Sodium borohydride → 2-(3-(Hydroxymethyl)-4-(1-methyl-5-(6-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1411496Notes

Reaction equation

HRID 1411496 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[N:11]=2)=[CH:5][C:4]([C:23]2[C:28]([CH:29]=[O:30])=[C:27]([N:31]3[CH2:43][CH2:42][N:34]4[C:35]5[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=5[CH:41]=[C:33]4[C:32]3=[O:44])[N:26]=[CH:25][CH:24]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:30][CH2:29][C:28]1[C:27]([N:31]2[CH2:43][CH2:42][N:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=4[CH:41]=[C:33]3[C:32]2=[O:44])=[N:26][CH:25]=[CH:24][C:23]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86684187HCID 86684187, compound

Product 1

HCID 866841892-(3-(Hydroxymethyl)-4-(1-methyl-5-(6-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the solution of 110b (60 mg, 0.1 mmol) in methanol (50 mL) was added sodium borohydride (11.5 mg, 0.3 mmol) at 0° C. and the mixture was stirred for another 30 minutes. Then the reaction mixture was quenched with water (3 mL) and concentrated. The residue was purified with reverse-phase prep-HPLC to afford 110 (26.2 mg, 49%). LCMS: [M+H]+ 595. 1H NMR (500 MHz, CDCl3) δ 8.69 (d, J=1.5, 1H), 8.46 (d, J=5.0, 1H), 7.97 (s, 1H), 7.80 (s, 1H), 7.41-7.37 (m, 1H), 7.34 (d, J=1.5, 1H), 6.89 (s, 1H), 6.22 (d, J=8.0, 1H), 6.15 (d, J=8.5, 1H), 5.10 (t, J=6.5, 1H), 4.66-4.64 (m, 1H), 4.51-4.30 (m, 2H), 4.15-4.12 (m, 2H), 3.93-3.89 (m, 1H), 3.71 (s, 3H), 3.58-3.48 (m, 4H), 2.61-2.56 (m, 7H), 2.47-2.39 (m, 3H), 1.91-1.87 (m, 2H), 1.79-1.78 (d, J=5.0, 3H)

Workup

  1. customThen the reaction mixture was quenched with water (3 mL)
  2. concentrationconcentrated
  3. customThe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-ebdc833a1bce43d1a3cc6ddff23d6444
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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