Sodium borohydride → 6-tert-butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-phthalazin-1(2H)-one

HRID 407616Notes

Reaction equation

HRID 407616 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[N:24]=[CH:23][CH:22]=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([N:38]5[CH2:43][CH2:42][N:41]([CH:44]6[CH2:47][O:46][CH2:45]6)[CH2:40][CH2:39]5)=[CH:34][N:33]=4)[C:28](=[O:48])[N:27]([CH3:49])[CH:26]=3)[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:19][OH:20])=[C:21]([C:25]3[CH:30]=[C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([N:38]5[CH2:39][CH2:40][N:41]([CH:44]6[CH2:47][O:46][CH2:45]6)[CH2:42][CH2:43]5)=[CH:34][N:33]=4)[C:28](=[O:48])[N:27]([CH3:49])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866839162-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 742239056-tert-butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-phthalazin-1(2H)-oneYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 103c (120 mg, 0.18 mmol), NaBH4 (21 mg, 0.54), and CH3OH (10 mL) was stirred at 25° C. for 1 h. It was then concentrated under reduced pressure and water (10 mL) was added. The resulting mixture was extracted with CH2Cl2 (10 mL×2). The combined CH2Cl2 extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 103 (45 mg, 38%). LCMS: [M+H]+ 667. 1H NMR (500 MHz, CDCl3) δ 8.66-8.68 (m, 2H), 8.35 (s, 1H), 7.96 (d, J=3.0, 1H), 7.81 (s, 1H), 7.65 (d, J=2.5, 1H), 7.55-7.59 (m, 3H), 6.83 (d, J=8.5, 1H), 4.71-4.74 (m, 4H), 4.51-4.52 (m, 2H), 4.07-4.08 (m, 1H), 3.73 (s, 3H), 3.56 (s, 1H), 3.20-3.22 (m, 4H), 2.56-2.58 (m, 4H), 1.59 (s, 9H)

Workup

  1. concentrationIt was then concentrated under reduced pressure and water (10 mL)
  2. additionwas added
  3. extractionThe resulting mixture was extracted with CH2Cl2 (10 mL×2)
  4. extractionThe combined CH2Cl2 extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-5a3087e6a5744be888fd73701905e425
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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