Sodium borohydride → 2-{3'-Hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-2,3,5,6,7,8-hexahydro-4H-2,4-b-diaza-fluoren-1-one

HRID 1021745Notes

Reaction equation

HRID 1021745 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:18][C@@H:17]3[CH3:26])=[CH:12][N:11]=2)=[CH:5][C:4]([C:27]2[C:32]([CH:33]=[O:34])=[C:31]([N:35]3[CH2:47][CH2:46][C:45]4[N:44]5[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]5)=[CH:38][C:37]=4[C:36]3=[O:48])[N:30]=[CH:29][CH:28]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:34][CH2:33][C:32]1[C:31]([N:35]2[CH2:47][CH2:46][C:45]3[N:44]4[C:39]([CH2:40][CH2:41][CH2:42][CH2:43]4)=[CH:38][C:37]=3[C:36]2=[O:48])=[N:30][CH:29]=[CH:28][C:27]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][O:24][CH2:23]4)[CH2:18][C@@H:17]3[CH3:26])=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86684263(S)-4-(1-Methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

Product 1

HCID 866842642-{3'-Hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4']bipyridinyl-2'-yl}-2,3,5,6,7,8-hexahydro-4H-2,4-b-diaza-fluoren-1-oneYield 63.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 149a (97 mg, 0.15 mmol), NaBH4 (17 mg, 0.45), and methanol (10 mL) was stirred at 25° C. for 1 h. The reaction mixture was then quenched with water (10 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 149 (62 mg, 63%). MS-ESI: [M+H]+ 651.3. 1H NMR (500 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.46 (d, J=5.0 Hz, 1H), 8.43 (s, 1H), 7.83 (d, J=3.0 Hz, 1H), 7.48 (d, J=2.0 Hz, 1H), 7.38-7.36 (m, 1H), 7.31 (J=5.0 Hz, 1H), 7.25-7.23 (m, 1H), 6.04 (s, 1H), 4.57-4.55 (m, 2H), 4.48-4.46 (m, 1H), 4.42-4.38 (m, 2H), 4.35-4.33 (m, 1H), 4.15-4.12 (m, 1H), 3.96-3.94 (m, 1H), 3.82-3.78 (m, 2H), 3.69-3.67 (m, 1H), 3.59 (s, 3H), 3.41-3.38 (m, 2H), 3.18-3.15 (m, 2H), 3.00-2.95 (m, 3H), 2.73-2.71 (m, 2H), 2.30-2.28 (m, 2H), 2.20-2.16 (m, 1H), 1.93-1.89 (m, 3H), 1.77-1.75 (m, 1H), 0.93 (d, J=6.5 Hz, 3H).

Workup

  1. customThe reaction mixture was then quenched with water (10 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-652747803b9a478b95ffe6557f868db3
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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