Water → 2-{5-[5-((S)-2-Ethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-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 1411652Notes

Reaction equation

HRID 1411652 reaction equation
[CH2:1]([CH:3]1[CH2:8][N:7]([CH:9]2[CH2:12][O:11][CH2:10]2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]2[C:25](=[O:26])[N:24]([CH3:27])[CH:23]=[C:22]([C:28]3[C:33]([CH:34]=[O:35])=[C:32]([N:36]4[CH2:48][CH2:47][C:46]5[N:45]6[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]6)=[CH:39][C:38]=5[C:37]4=[O:49])[N:31]=[CH:30][CH:29]=3)[CH:21]=2)=[N:17][CH:18]=1)[CH3:2].[BH4-].[Na+].O>CO>[CH2:1]([C@H:3]1[CH2:8][N:7]([CH:9]2[CH2:10][O:11][CH2:12]2)[CH2:6][CH2:5][N:4]1[C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:20]2[C:25](=[O:26])[N:24]([CH3:27])[CH:23]=[C:22]([C:28]3[CH:29]=[CH:30][N:31]=[C:32]([N:36]4[CH2:48][CH2:47][C:46]5[N:45]6[C:40]([CH2:41][CH2:42][CH2:43][CH2:44]6)=[CH:39][C:38]=5[C:37]4=[O:49])[C:33]=3[CH2:34][OH:35])[CH:21]=2)=[N:17][CH:18]=1)[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 866842854-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-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 715571082-{5-[5-((S)-2-Ethyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-3'-hydroxymethyl-1-methyl-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 81.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 161g (120 mg, 0.18 mmol) in methanol (20 mL) was added NaBH4 (21 mg, 0.54 mmol) at room temperature. After the reaction was stirred for 1 h, LCMS indicated the reaction was complete. Then the mixture was poured into water (20 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×40 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue solid was purified by prep-HPLC to afford 161 (97 mg, 81%) as white solid. MS-ESI: [M+H]+ 665. 1H NMR (500 MHz, CDCl3) δ 8.63 (s, 1H), 8.50 (d, J=5.0 Hz, 1H), 7.93 (s, 1H), 7.84-7.82 (m, 2H), 7.35 (d, J=4.5 Hz, 1H), 7.28 (s, 1H), 6.82 (d, J=9.0 Hz, 1H), 6.32 (s, 1H), 5.01-4.99 (m, 1H), 4.73-4.64 (m, 5H), 4.45-4.40 (m, 1H), 4.30 (t, J=12.0 Hz, 1H), 3.94-3.91 (m, 1H), 3.85-3.83 (m, 2H), 3.72 (s, 3H), 3.55-3.53 (m, 1H), 3.34-3.32 (m, 1H), 3.14-3.12 (m, 2H), 3.04-2.92 (m, 2H), 2.84-2.82 (m, 2H), 2.59-2.57 (m, 1H), 2.46-2.44 (m, 2H), 2.38-2.36 (m, 1H), 2.06-2.01 (m, 2H), 1.90-1.86 (m, 2H), 1.68-1.66 (m, 1H), 1.43-1.39 (m, 1H), 0.82 (t, J=7.5 Hz, 3H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with dichloromethane (3×40 mL)
  3. washThe combined organic layer was washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue solid was purified by prep-HPLC

Sources & evidence

ORD record
ord-89d69653a8d046d59a31c30ea1b0b76d
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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