Sodium borohydride → 2-[5-(6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-3'-hydroxymethyl-1-methyl-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 1411673Notes

Reaction equation

HRID 1411673 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:18]=[C:13]3[CH2:14][O:15][CH2:16][CH2:17][N:12]3[N:11]=2)=[CH:5][C:4]([C:19]2[C:24]([CH:25]=[O:26])=[C:23]([N:27]3[CH2:38][CH2:37][N:36]4[C:29](=[CH:30][C:31]5[CH2:32][C:33]([CH3:40])([CH3:39])[CH2:34][C:35]=54)[C:28]3=[O:41])[N:22]=[CH:21][CH:20]=2)=[CH:3]1.[BH4-].[Na+]>CO>[N:11]1[N:12]2[C:13]([CH2:14][O:15][CH2:16][CH2:17]2)=[CH:18][C:10]=1[NH:9][C:6]1[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=[C:4]([C:19]2[CH:20]=[CH:21][N:22]=[C:23]([N:27]3[CH2:38][CH2:37][N:36]4[C:35]5[CH2:34][C:33]([CH3:40])([CH3:39])[CH2:32][C:31]=5[CH:30]=[C:29]4[C:28]3=[O:41])[C:24]=2[CH2:25][OH:26])[CH:5]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866842974-(1-Methyl-5-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-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 715572742-[5-(6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-3'-hydroxymethyl-1-methyl-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 26.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 168b (200 mg, 0.36 mmol) at 0° C. in methanol (10 mL) was added sodium borohydride (42 mg, 1.1 mmol). The reaction mixture was stirred for 30 minutes and quenched with water (2 mL). It was then concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 168 (53 mg, 21%) as a yellow solid. MS-ESI: [M+H]+ 556.6. 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J=5.2 Hz, 1H), 7.97 (d, J=2.4 Hz, 1H), 7.71 (d, J=2.0 Hz, 1H), 7.45 (s, 1H), 7.33 (d, J=5.2 Hz, 1H), 6.83 (s, 1H), 5.71 (s, 1H), 5.04-5.01 (m, 1H), 4.78 (s, 2H), 4.64-4.62 (m, 1H), 4.49 (d, J=2.8 Hz, 1H), 4.32-4.28 (m, 1H), 4.14 (d, J=4.4 Hz, 2H), 4.09-4.08 (m, 4H), 3.87-3.83 (m, 1H), 3.70 (s, 3H), 2.56 (d, J=2.8 Hz, 2H), 2.50 (s, 2H), 1.26 (s, 6H).

Workup

  1. customquenched with water (2 mL)
  2. concentrationIt was then concentrated under reduced pressure
  3. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-21ec78d363ba44cdb1ae59ea0a3bf4c4
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

Loading…