Sodium borohydride → 2-(4-(Hydroxymethyl)-5-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 1021722Notes

Reaction equation

HRID 1021722 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[CH:27]=[N:26][CH:25]=[C:24]([N:28]3[CH2:40][CH2:39][N:31]4[C:32]5[CH2:33][CH2:34][CH2:35][CH2:36][C:37]=5[CH:38]=[C:30]4[C:29]3=[O:41])[C:21]=2[CH:22]=[O:23])=[CH:3]1.[BH4-].[Na+]>CO>[OH:23][CH2:22][C:21]1[C:20]([C:4]2[CH:5]=[C:6]([NH:9][C:10]3[CH:19]=[C:13]4[CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][N:12]4[N:11]=3)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=2)=[CH:27][N:26]=[CH:25][C:24]=1[N:28]1[CH2:40][CH2:39][N:31]2[C:32]3[CH2:33][CH2:34][CH2:35][CH2:36][C:37]=3[CH:38]=[C:30]2[C:29]1=[O:41]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866842443-(1-Methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 866842452-(4-(Hydroxymethyl)-5-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 85%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 138a (200 mg, 0.36 mmol) and NaBH4 (50 mg, 1.2 mmol) in MeOH (60 mL) was stirred at room temperature for 2 h. The mixture was quenched with water and extracted with EtOAc (10 mL×3). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 138 (162 mg, 85%). LCMS: [M+H]+: 555.3. 1H NMR (500 MHz, CDCl3) δ 8.64 (s, 1H), 8.49 (s, 1H), 7.97 (d, J=2.5, 1H), 7.42 (s, 1H), 7.33 (d, J=2, 1H), 6.88 (s, 1H), 5.68 (s, 1H), 4.65-4.63 (m, 1H), 4.57-4.55 (m, 1H), 4.37 (t, J=11, 1H), 4.20-4.16 (m, 3H), 4.07-3.98 (m, 3H), 3.70 (s, 3H), 3.59 (s, 2H), 2.87 (t, J=5.5, 2H), 2.61-2.56 (m, 4H), 2.48 (s, 3H), 1.92-1.90 (m, 2H), 1.80-1.79 (m, 2H)

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with EtOAc (10 mL×3)
  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-0097820b96bf44b396740351d24d155c
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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