Sodium borohydride → 2-{3-Hydroxymethyl-4-[6-(imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-pyridin-2-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one

HRID 1021841Notes

Reaction equation

HRID 1021841 reaction equation
[CH3:1][C:2]1([CH3:41])[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[N:24]=[C:25]([NH:31][C:32]6[CH:37]=[CH:36][N:35]7[CH:38]=[CH:39][N:40]=[C:34]7[CH:33]=6)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=5)[CH:18]=[CH:17][N:16]=4)[C:9]3=[O:14])[C:4]=2[CH2:3]1.[BH4-].[Na+]>CO>[OH:22][CH2:21][C:20]1[C:15]([N:8]2[CH2:7][CH2:6][N:5]3[C:4]4[CH2:3][C:2]([CH3:1])([CH3:41])[CH2:13][C:12]=4[CH:11]=[C:10]3[C:9]2=[O:14])=[N:16][CH:17]=[CH:18][C:19]=1[C:23]1[N:24]=[C:25]([NH:31][C:32]2[CH:37]=[CH:36][N:35]3[CH:38]=[CH:39][N:40]=[C:34]3[CH:33]=2)[C:26](=[O:30])[N:27]([CH3:29])[CH:28]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866843332-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(6-{imidazo[1,2-a]pyridin-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehyde

Product 1

HCID 865673222-{3-Hydroxymethyl-4-[6-(imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-pyridin-2-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-oneYield 61%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 185c (80 mg, 0.146 mmol) in methanol (5 mL) was added NaBH4 (34 mg, 0.90 mmol) at room temperature. After the reaction was stirred for 1 h, LCMS indicated the reaction was complete. The reaction mixture was quenched with water (3 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×10 mL). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 185 (49 mg, 61%) as light yellow solid. MS-ESI: [M+H]+ 551. 1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.57 (d, J=10.5 Hz, 1H), 8.51 (s, 1H), 8.41 (d, J=7.0 Hz, 1H), 7.77 (s, 1H), 7.75 (s, 1H), 7.63 (s, 1H), 7.46 (d, J=6.0 Hz, 1H), 7.42 (s, 1H), 6.59 (s, 1H), 5.04-5.02 (m, 1H), 4.67-4.64 (m, 1H), 4.519-4.481 (m, 1H), 4.31-4.20 (m, 3H), 3.88 (d, J=7.0 Hz, 1H), 3.58 (s, 3H), 2.63-2.55 (m, 2H), 2.44-2.42 (m, 2H), 1.23 (s, 6H).

Workup

  1. customThe reaction mixture was quenched with water (3 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (3×10 mL)
  4. washThe combined organic layer was washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-9e763d6b7af34aa9a956f4930f398e91
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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