Acetic Acid → N-(2-aminophenyl)-4-(3-cyano-5-{[methyl(tetrahydrofuran-2-ylmethyl)amino]methyl}pyridin-2-yl)benzamide

HRID 599517Notes

Reaction equation

HRID 599517 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:33])[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([C:29]#[N:30])=[CH:27][C:26](C=O)=[CH:25][N:24]=2)=[CH:19][CH:18]=1)=O)(C)(C)C.[CH3:34][NH:35][CH2:36][CH:37]1[O:41][CH2:40][CH2:39][CH2:38]1.[C:42](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C(O)=O>O1CCCC1.ClCCl>[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:33])[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([C:29]#[N:30])=[CH:27][C:26]([CH2:34][N:35]([CH3:42])[CH2:36][CH:37]3[CH2:38][CH2:39][CH2:40][O:41]3)=[CH:25][N:24]=2)=[CH:19][CH:18]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 98090N-(Tetrahydrofurfuryl)-N-methylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86624985HCID 86624985, compound

Product 1

HCID 59848779N-(2-aminophenyl)-4-(3-cyano-5-{[methyl(tetrahydrofuran-2-ylmethyl)amino]methyl}pyridin-2-yl)benzamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.20 g, 0.45 mmol; prepared as described in Method 15 below), N-methyltetrahydrofurfurylamine (81 mg, 0.7 mmol) and acetic acid (26 μl, 0.45 mmol) were dissolved in tetrahydrofuran (5 ml). The mixture was stirred at ambient temperature for 1 hour. Sodium triacetoxyborohydride (144 mg, 0.7 mmol) was then added and the mixture stirred for a further 3 hours. The mixture was concentrated and the residue purified by flash chromatography eluting with 100% ethyl acetate. Concentration of the solvent gave product as a gum. This was dissolved in dichloromethane (6 ml), trifluoroacetic acid (1.2 ml) was added and the solution then stirred at ambient temperature for 2 hours. The resulting solution was absorbed onto an SCX-2 column, which was washed with methanol (3 column volumes) and the product eluted with a 2M solution of ammonia in methanol (3 column volumes) then concentrated to give the product as a gum. This was re-precipitated by stirring in diethyl ether (3 ml) to give the title compound as a foam/gum (43 mg, 22%). NMR Spectrum: (DMSO-d6, 373K) 1H NMR 1.53 (m, 1H), 1.82 (m, 2H), 1.98 (m, 1H), 2.37 (s, 3H), 2.64 (m, 2H), 3.00 (br s, 2H), 3.66 (q, 1H), 3.77 (q, 1H), 3.84 (m, 2H), 4.04 (m, 1H), 6.63 (m, 1H), 6.82 (d, 1H), 6.98 (m, 1H), 7.27 (d, 1H), 8.00 (d, 2H), 8.14 (d, 2H), 8.29 (s, 1H), 8.89 (s, 1H), 9.50 (br s, 1H); Mass Spectrum: M+H+ 442.

Workup

  1. stirringthe mixture stirred for a further 3 hours
  2. concentrationThe mixture was concentrated
  3. customthe residue purified by flash chromatography
  4. washeluting with 100% ethyl acetate
  5. customConcentration of the solvent gave product as a gum
  6. stirringthe solution then stirred at ambient temperature for 2 hours
  7. customThe resulting solution was absorbed onto an SCX-2 column, which
  8. washwas washed with methanol (3 column volumes)
  9. washthe product eluted with a 2M solution of ammonia in methanol (3 column volumes)
  10. concentrationthen concentrated

Sources & evidence

ORD record
ord-16065a91bbd64352a675f461fb72339c
Source dataset
uspto-grants-2011_03
Patent number
US07897778B2

Reaction notes

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