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

HRID 592629Notes

Reaction equation

HRID 592629 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:18][CH2:17]3)=[CH:12][N:11]=2)=[CH:5][C:4]([C:26]2[CH:33]=[N:32][CH:31]=[C:30]([N:34]3[CH:46]=[CH:45][N:37]4[C:38]5[CH2:39][CH2:40][CH2:41][CH2:42][C:43]=5[CH:44]=[C:36]4[C:35]3=[O:47])[C:27]=2[CH:28]=[O:29])=[CH:3]1.[BH4-].[Na+]>CO>[OH:29][CH2:28][C:27]1[C:26]([C:4]2[CH:5]=[C:6]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][N:19]([CH:22]5[CH2:25][O:24][CH2:23]5)[CH2:20][CH2:21]4)=[CH:12][N:11]=3)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=2)=[CH:33][N:32]=[CH:31][C:30]=1[N:34]1[CH:46]=[CH:45][N:37]2[C:38]3[CH2:39][CH2:40][CH2:41][CH2:42][C:43]=3[CH:44]=[C:36]2[C:35]1=[O:47]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866842243-(1-Methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-5-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)isonicotinaldehyde

Product 1

HCID 866842252-(4-(Hydroxymethyl)-5-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)-6,7,8,9-tetrahydropyrazino[1,2-a]indol-1(2H)-oneYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 126b (76 mg, 0.12 mmol) at 0° C. in methanol (4 mL) was added sodium borohydride (20 mg, 0.7 mmol) and the mixture was stirred for 30 minutes. Then the reaction mixture was quenched with water (1.0 mL) and concentrated. The residue was purified by reverse-phase prep-HPLC to afford 126 (28 mg, 37%). LCMS: [M+H]+ 635. 1H NMR (500 MHz, DMSO) δ 8.61 (d, J=2.5, 1H), 8.59 (s, 1H), 8.50 (s, 1H), 8.43 (s, 1H), 7.86 (d, J=3.0, 1H), 7.38-7.36 (m, 2H), 7.27-7.22 (m, 2H), 6.82-6.78 (m, 2H), 5.18-5.11 (m, 1H), 4.55 (t, J=6.0, 2H), 4.45 (t, J=6.0, 2H), 4.41-4.29 (m, 2H), 3.60 (s, 3H), 3.44-3.42 (m, 1H), 3.06 (t, J=4.5, 4H), 2.75-2.73 (m, 2H), 2.62-2.60 (m, 2H), 2.38 (t, J=4.5, 4H), 1.86-1.75 (m, 4H).

Workup

  1. customThen the reaction mixture was quenched with water (1.0 mL)
  2. concentrationconcentrated
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-4dcdd8ae7f1b4961a3e82b5272e231b1
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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