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 1411696Notes

Reaction equation

HRID 1411696 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-b81fc0813c6e43fea7c9577a0721f4b6
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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