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 592738Notes

Reaction equation

HRID 592738 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-e17f369903d1468ca39e31199136eae0
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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