Sodium borohydride → 6-tert-Butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(5-(5-isopropyl-6-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)phthalazin-1(2H)-one

HRID 407798Notes

Reaction equation

HRID 407798 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:44]=[C:35]5[CH2:36][N:37]([CH:41]([CH3:43])[CH3:42])[C:38](=[O:40])[CH2:39][N:34]5[N:33]=4)[C:28](=[O:45])[N:27]([CH3:46])[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:44]=[C:35]5[CH2:36][N:37]([CH:41]([CH3:42])[CH3:43])[C:38](=[O:40])[CH2:39][N:34]5[N:33]=4)[C:28](=[O:45])[N:27]([CH3:46])[CH:26]=3)[CH:22]=[CH:23][N:24]=1)[N:9]=[CH:8]2)([CH3:2])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866840592-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-isopropyl-6-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Product 1

HCID 866840586-tert-Butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(5-(5-isopropyl-6-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)phthalazin-1(2H)-oneYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 25-mL single-neck round-bottomed flask was charged with 151h (90 mg, 0.14 mmol), NaBH4 (18 mg, 0.42 mmol), and methanol (5 mL). The mixture was stirred at room temperature for 1 h and concentrated under reduced pressure. To the resulting residue was added water (10 mL) and the mixture was extracted with dichloromethane (3×15 mL). The combined organic layer was concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 151 (50 mg, 55%). MS-ESI: [M+H]+ 626.8. 1H NMR (500 MHz, CDCl3) δ 8.67 (d, J=5.0 Hz, 1H), 8.36 (d, J=2.5 Hz, 1H), 8.02 (d, J=2.0 Hz, 1H), 7.59-7.58 (m, 3H), 7.55-7.52 (m, 2H), 5.90 (s, 1H), 5.07-5.05 (m, 1H), 4.74 (s, 2H), 4.50-4.47 (m, 4H), 4.09-4.06 (m, 1H), 3.73 (s, 3H), 1.45 (s, 9H), 1.26 (d, J=7.0 Hz, 6H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionTo the resulting residue was added water (10 mL)
  3. extractionthe mixture was extracted with dichloromethane (3×15 mL)
  4. concentrationThe combined organic layer was concentrated under reduced pressure
  5. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-1184c2b598d340f5beed5d4e87d64d1e
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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