Sodium borohydride → 6-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 407650Notes

Reaction equation

HRID 407650 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[S:33][C:34]5[CH2:35][N:36]([CH3:41])[CH2:37][CH2:38][C:39]=5[N:40]=4)[C:28](=[O:42])[N:27]([CH3:43])[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[S:33][C:34]5[CH2:35][N:36]([CH3:41])[CH2:37][CH2:38][C:39]=5[N:40]=4)[C:28](=[O:42])[N:27]([CH3:43])[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 866839372-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 866839396-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 38.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

To a mixture of 115d (100 mg, 0.15 mmol) in methanol (6 mL) was added NaBH4 (18 mg, 0.45 mmol). The mixture was stirred at 30° C. for 1 h and then quenched with water (10 mL). It was extracted with dichloromethane (3×30 mL) and the combined organic layer was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 115 (35 mg, 36%) as a white solid. MS-ESI: [M+H]+ 602.2. 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J=5.0 Hz, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.35 (d, J=2.5 Hz, 1H), 8.30 (s, 1H), 7.77 (d, J=2.0 Hz, 1H), 7.58-7.53 (m, 3H), 4.49-4.45 (m, 2H), 4.10 (bs, 1H), 3.73 (s, 3H), 3.58 (s, 2H), 2.83-2.79 (m, 4H), 2.52 (s, 3H), 1.45 (s, 9H).

Workup

  1. customquenched with water (10 mL)
  2. extractionIt was extracted with dichloromethane (3×30 mL)
  3. concentrationthe combined organic layer was concentrated under reduced pressure
  4. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-c251616c00c244a1a221f1558a85b4df
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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