Tetrabutylammonium Fluoride → HCID 58345120, compound

HRID 1887997Notes

Reaction equation

HRID 1887997 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:31]([C:32]3[CH:47]=[CH:46][C:35]([CH2:36][NH:37][C:38](=[O:45])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:34][CH:33]=3)[C:11]3=[N:12][CH:13]=[C:14]([C:16]4[CH:20]=[CH:19][N:18]([Si](C(C)C)(C(C)C)C(C)C)[CH:17]=4)[CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.O.ClCCl.CO>[NH2:1][C:2]1[C:7]([C:8]2[N:31]([C:32]3[CH:47]=[CH:46][C:35]([CH2:36][NH:37][C:38](=[O:45])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:34][CH:33]=3)[C:11]3=[N:12][CH:13]=[C:14]([C:16]4[CH:20]=[CH:19][NH:18][CH:17]=4)[CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67311536HCID 67311536, compound

Product 1

HCID 58345120HCID 58345120, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

N-(4-(2-(2-aminopyridin-3-yl)-6-(1H-pyrrol-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide was synthesized according to General Procedure A followed by General Procedures I, B and C and subsequent TBAF-deprotection. TBAF-deprotection: To a solution of N-(4-(2-(2-aminopyridin-3-yl)-6-(1-(triisopropylsilyl)-1H-pyrrol-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)benzamide (5.2 g) in anhydrous tetrahydrofuran (100 ml) was added 1.0 M tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (3 ml). The reaction was stirred at room temperature for 1 hour. The reaction was diluted with water (300 ml), dichloromethane (200 ml) and methanol (50 ml) and stirred for 1 hour. The organics were separated and the aqueous was washed with dichloromethane (1×200 ml). The organics were combined, washed with water (2×200 ml), brine (1×100 ml), dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (30% ethyl acetate in dichloromethane to 5% methanol/25% ethyl acetate in dichloromethane) gave the product as a yellow solid. Further trituration with ether and hexanes gave a light yellow solid (1.2 g, 41%). 400 M Hz 1H NMR (DMSO-d6) δ: 11.02 (s, 1H), 9.17-9.11 (m, 1H), 8.55 (s, 1H), 8.29 (s, 1H), 8.00-7.96 (m, 1H), 7.93 (d, J=7.6 Hz, 2H), 7.58-7.33 (m, 8H), 7.21 (d, J=7.6 Hz, 1H), 7.04 (s, 2H), 6.85 (s, 1H), 6.56 (s, 1H), 6.40 (t, J=6.0 Hz, 1H), 4.58 (d, J=6.0 Hz, 2H); LCMS: 486 [M+H]. Calc. for C29H23N7O 0.18 water 0.02 ethyl acetate 0.08 dichloromethane: C, 70.42; H, 4.80; N, 19.71. Found C, 70.41; H, 4.78; N, 19.71.

Workup

  1. stirringstirred for 1 hour
  2. customThe organics were separated
  3. washthe aqueous was washed with dichloromethane (1×200 ml)
  4. washwashed with water (2×200 ml), brine (1×100 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (30% ethyl acetate in dichloromethane to 5% methanol/25% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-4a97d3268a5245f2b0c3ca128db20959
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

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