Sodium borohydride → 2-[3'-Hydroxymethyl-1-methyl-5-(2-methyl-pyrimidin-4-ylamino)-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 592761Notes

Reaction equation

HRID 592761 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[N:11]=2)=[CH:5][C:4]([C:17]2[C:22]([CH:23]=[O:24])=[C:21]([N:25]3[CH2:36][CH2:35][N:34]4[C:27](=[CH:28][C:29]5[CH2:30][C:31]([CH3:38])([CH3:37])[CH2:32][C:33]=54)[C:26]3=[O:39])[N:20]=[CH:19][CH:18]=2)=[CH:3]1.[BH4-].[Na+]>CO.ClCCl>[OH:24][CH2:23][C:22]1[C:21]([N:25]2[CH2:36][CH2:35][N:34]3[C:33]4[CH2:32][C:31]([CH3:37])([CH3:38])[CH2:30][C:29]=4[CH:28]=[C:27]3[C:26]2=[O:39])=[N:20][CH:19]=[CH:18][C:17]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([CH3:16])[N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866843204-(1-Methyl-5-(2-methylpyrimidin-4-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl)nicotinaldehyde

Product 1

HCID 865673202-[3'-Hydroxymethyl-1-methyl-5-(2-methyl-pyrimidin-4-ylamino)-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 69%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 179a (262 mg, 0.50 mmol) in methanol/dichloromethane (10/10 mL) was added NaBH4 (57 mg, 1.5 mmol) at room temperature. After the reaction was stirred for 1 h, LCMS indicated the reaction was complete. Then the mixture was concentrated under reduced pressure. The residue was diluted with water (5 mL) and dichloromethane (20 mL. The water phase was separated and 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 solid was purified by reverse-phase prep-HPLC to afford 179 (180 mg, 69%) as white solid. MS-ESI: [M+H]+ 526. 1H NMR (500 MHz, CDCl3) δ 8.93 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.5 Hz, 1H), 8.28 (d, J=5.5 Hz, 1H), 8.07 (s, 1H), 8.03 (d, J=2.0 Hz, 1H), 7.36 (s, 1H), 6.86 (s, 1H), 6.60 (d, J=6.0 Hz, 1H), 5.18-5.16 (m, 1H), 4.70-4.67 (m, 1H), 4.55-4.53 (m, 1H), 4.33-4.31 (m, 1H), 4.18-4.16 (m, 2H), 3.91-3.90 (m, 1H), 3.74 (s, 3H), 2.60 (s, 3H), 2.58 (d, J=5.5 Hz, 2H), 2.52 (s, 2H), 1.28 (s, 6H).

Workup

  1. concentrationThen the mixture was concentrated under reduced pressure
  2. additionThe residue was diluted with water (5 mL) and dichloromethane (20 mL
  3. customThe water phase was separated
  4. extractionextracted with dichloromethane (3×10 mL)
  5. washThe combined organic layer was washed with brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue solid was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-72b67c1cf3804a3e90f5904ee81b7961
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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