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

HRID 407803Notes

Reaction equation

HRID 407803 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:41]=[C:35]5[CH2:36][N:37]([CH3:40])[CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:42])[N:27]([CH3:43])[N: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:41]=[C:35]5[CH2:36][N:37]([CH3:40])[CH2:38][CH2:39][N:34]5[N:33]=4)[C:28](=[O:42])[N:27]([CH3:43])[N: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 866840622-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)nicotinaldehyde

Product 1

HCID 712578706-tert-butyl-8-fluoro-2-(3-(hydroxymethyl)-4-(1-methyl-5-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-2-yl)phthalazin-1(2H)-oneYield 21%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 153c (170 mg, 0.29 mmol) and NaBH4(20 mg, 0.50 mmol) in methanol (5 mL) was stirred at room temperature for 0.5 h. The reaction mixture was then quenched with water (7 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford the 153 as a pale yellow solid (35 mg, 21%). MS-ESI: [M+H]+ 586.3. 1H NMR (500 MHz, DMSO-d6) δ 9.39 (s, 1H), 8.63 (d, J=5.0 Hz, 1H), 8.54 (d, J=2.0 Hz 1H), 7.93 (s, 1H), 7.90 (d, J=2.0 Hz, 1H), 7.77 (dd, J=1.5, 12.5 Hz, 1H), 7.60-7.59 (m, 1H), 6.03 (s, 1H), 4.82-4.81 (m, 1H), 4.51-4.45 (m, 2H), 4.01-3.98 (m, 2H), 3.77 (s, 3H), 3.62-3.60 (m, 2H), 2.90-2.86 (m, 2H), 2.42-2.40 (m, 3H), 1.34 (s, 9H).

Workup

  1. customThe reaction mixture was then quenched with water (7 mL)
  2. concentrationconcentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (2×10 mL)
  4. extractionThe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-a482c21cf9194250ab33b1f9a3d73e41
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

Loading…