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

HRID 1411461Notes

Reaction equation

HRID 1411461 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]([CH3:22])[CH2:18][CH2:17]3)=[CH:12][N:11]=2)=[CH:5][C:4]([C:23]2[CH:30]=[N:29][CH:28]=[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])[C:24]=2[CH:25]=[O:26])=[CH:3]1.[BH4-].[Na+]>CO>[OH:26][CH2:25][C:24]1[C:23]([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]([CH3:22])[CH2:20][CH2:21]4)=[CH:12][N:11]=3)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=2)=[CH:30][N:29]=[CH:28][C:27]=1[N:31]1[CH2:43][CH2:42][N:34]2[C:35]3[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=3[CH:41]=[C:33]2[C:32]1=[O:44]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866841713-(1-Methyl-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-5-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)isonicotinaldehyde

Product 1

HCID 715588532-(4-(Hydroxymethyl)-5-(1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 20%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-5-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)isonicotinaldehyde 102b (135 mg, 0.22 mmol) and NaBH4 (20 mg, 0.5 mmol) in MeOH (5 mL) was stirred at 0° C. for 0.5 h. The mixture was quenched with water and the residue was extracted with EtOAc (5 mL×2). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 102 (18 mg, 20%). LCMS: [M+H]+ 595. 1H NMR (500 MHz, DMSO) δ 8.59 (s, 1H), 8.55 (s, 1H), 8.49 (s, 1H), 8.45 (s, 1H), 7.87 (s, 1H), 7.37-7.38 (m, 2H), 7.23-7.25 (m, 1H), 6.54 (s, 1H), 5.16 (t, J=3.0, 1H), 4.40 (s, 2H), 4.14-4.18 (m, 3H), 3.93-3.95 (m, 1H), 3.60 (s, 3H), 3.09 (s, 4H), 2.60-2.61 (m, 6H), 2.48-2.34 (m, 5H), 1.78-1.79 (m, 2H), 1.69-1.70 (m, 2H)

Workup

  1. customThe mixture was quenched with water
  2. extractionthe residue was extracted with EtOAc (5 mL×2)
  3. extractionThe combined EtOAc extract
  4. concentrationwas concentrated under reduced pressure
  5. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-2c7e4e9c12234609ad47f6621127c366
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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