Water → 10-Fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 1021718Notes

Reaction equation

HRID 1021718 reaction equation
[F:1][C:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]2[CH2:11][CH2:12][N:13]([C:16]3[N:23]=[CH:22][CH:21]=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:40]=[C:34]6[CH2:35][N:36]([CH3:39])[CH2:37][CH2:38][N:33]6[N:32]=5)[C:27](=[O:41])[N:26]([CH3:42])[CH:25]=4)[C:17]=3[CH:18]=[O:19])[C:14](=[O:15])[C:3]=12.[BH4-].[Na+].O>CO>[F:1][C:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]2[CH2:11][CH2:12][N:13]([C:16]3[C:17]([CH2:18][OH:19])=[C:20]([C:24]4[CH:29]=[C:28]([NH:30][C:31]5[CH:40]=[C:34]6[CH2:35][N:36]([CH3:39])[CH2:37][CH2:38][N:33]6[N:32]=5)[C:27](=[O:41])[N:26]([CH3:42])[CH:25]=4)[CH:21]=[CH:22][N:23]=3)[C:14](=[O:15])[C:3]=12

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 866842402-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 8668424110-Fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 135b (280 g, 0.49 mmol) in MeOH (50 mL) was added NaBH4 (56 g, 1.47 mmol) at room temperature. After the reaction was stirred for 3 h, LCMS indicated the reaction was completed. Then the mixture was poured into H2O (50 mL) and extracted with DCM (50 mL×3). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by reverse-phase prep-HPLC to afford 135 (187 mg, 67%) as a white solid. MS: [M+H]+ 572. 1H NMR (500 MHz, CDCl3) δ 8.47 (d, J=5.5, 1H), 7.95 (d, J=2.0, 1H), 7.70 (d, J=2.0, 1H), 7.42 (s, 1H), 7.35 (d, J=5.5, 1H), 5.70 (s, 1H), 4.96 (t, J=7.0, 1H), 4.62 (s, 1H), 4.45 (s, 1H), 4.33 (s, 1H), 4.07-4.12 (m, 4H), 3.84 (s, 1H), 3.70 (s, 3H), 3.60 (s, 2H), 2.88 (t, J=5.5, 2H), 2.61 (s, 2H), 2.57 (s, 2H), 2.48 (s, 3H), 1.86-1.90 (m, 2H), 1.77 (s, 2H)

Workup

  1. extractionextracted with DCM (50 mL×3)
  2. washThe combined organic layer was washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-58552fb6de0e42dbae2df8ca01fa4004
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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