Sodium borohydride → 2-{5-[5-((S)-2-Ethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one

HRID 1021788Notes

Reaction equation

HRID 1021788 reaction equation
[CH3:1][C:2]1([CH3:50])[CH2:13][C:12]2[CH:11]=[C:10]3[N:5]([CH2:6][CH2:7][N:8]([C:15]4[C:20]([CH:21]=[O:22])=[C:19]([C:23]5[CH:28]=[C:27]([NH:29][C:30]6[CH:35]=[CH:34][C:33]([N:36]7[CH2:41][CH2:40][N:39]([CH:42]8[CH2:45][O:44][CH2:43]8)[CH2:38][C@@H:37]7[CH2:46][CH3:47])=[CH:32][N:31]=6)[C:26](=[O:48])[N:25]([CH3:49])[CH:24]=5)[CH:18]=[CH:17][N:16]=4)[C:9]3=[O:14])[C:4]=2[CH2:3]1.[BH4-].[Na+]>CO>[CH2:46]([C@H:37]1[CH2:38][N:39]([CH:42]2[CH2:43][O:44][CH2:45]2)[CH2:40][CH2:41][N:36]1[C:33]1[CH:34]=[CH:35][C:30]([NH:29][C:27]2[C:26](=[O:48])[N:25]([CH3:49])[CH:24]=[C:23]([C:19]3[CH:18]=[CH:17][N:16]=[C:15]([N:8]4[CH2:7][CH2:6][N:5]5[C:4]6[CH2:3][C:2]([CH3:50])([CH3:1])[CH2:13][C:12]=6[CH:11]=[C:10]5[C:9]4=[O:14])[C:20]=3[CH2:21][OH:22])[CH:28]=2)=[N:31][CH:32]=1)[CH3:47]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866842882-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[5-({5-[(2S)-2-ethyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde

Product 1

HCID 865672612-{5-[5-((S)-2-Ethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-oneYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 164a (200 mg, 0.30 mmol) and NaBH4 (36 mg, 0.90 mmol) in methanol (30 mL) was stirred at 30° C. for 2 h. The mixture was quenched with water and concentrated under reduced pressure. The residue was extracted with ethyl acetate (3×10 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 164 (140 mg, 72%) as light green solid. MS-ESI: [M+H]+ 679.3. 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J=2.5 Hz, 1H), 8.49 (d, J=5.0 Hz, 1H), 7.93 (d, J=2.5 Hz, 1H), 7.83 (s, 1H), 7.82 (s, 1H), 7.37 (d, J=5.0 Hz, 1H), 7.27 (s, 1H), 6.85 (s, 1H), 6.82 (d, J=9.0 Hz, 1H), 5.06 (s, 1H), 4.71-4.61 (m, 5H), 4.52-4.50 (m, 1H), 4.34-4.32 (m, 1H), 4.16 (d, J=4.5 Hz, 2H), 3.87-3.85 (m, 1H), 3.72 (s, 3H), 3.55-3.50 (m, 1H), 3.33-3.30 (m, 1H), 3.12 (t, J=5.0 Hz, 2H), 2.58-2.55 (m, 3H), 2.52 (s, 2H), 2.44 (d, J=3.5 Hz, 2H), 2.35 (t, J=5.5 Hz, 1H), 1.68-1.64 (m, 1H), 1.42-1.37 (m, 1H), 1.28 (s, 6H), 0.82 (t, J=7.5 Hz, 3H).

Workup

  1. customThe mixture was quenched with water
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with ethyl acetate (3×10 mL)
  4. extractionThe combined ethyl acetate extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-5742998eb3ec4c3e8ce580d3285c64a8
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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