Ethylamine → t-Butyl {2-[(4-{3-cyano-5-[(ethylamino)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

HRID 599512Notes

Reaction equation

HRID 599512 reaction equation
[C:1]([O:5][C:6]([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]([CH:31]=O)=[CH:25][N:24]=2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34]([NH2:36])[CH3:35].[BH4-].[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O.CO>[C:29]([C:28]1[C:23]([C:20]2[CH:19]=[CH:18][C:17]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:33])=[CH:22][CH:21]=2)=[N:24][CH:25]=[C:26]([CH2:31][NH:36][CH2:34][CH3:35])[CH:27]=1)#[N:30]

Participants

10

Reactant 4

HCID 6341EthylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 86624985HCID 86624985, compound

Product 1

HCID 86624987t-Butyl {2-[(4-{3-cyano-5-[(ethylamino)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

Reagents, catalysts & solvents 5

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(2-t-Butoxycarbonylaminophenyl)-4-(3-cyano-5-formylpyridin-2-yl)benzamide (0.80 g, 1.8 mmol; prepared as described in Method 15 below) and ethylamine (1.4 ml of a 1.0M solution in THF, 1.4 mmol) were dissolved in dichloromethane (15 ml). Titanium (IV) isopropoxide (1.55 g, 1.62 ml, 5.4 mmol) was added and the mixture stirred at ambient temperature for 1 hour. Sodium borohydride (342 mg) and methanol (3 ml) were then added and the mixture stirred for a further 30 minutes. Water (20 ml) then a saturated aqueous sodium bicarbonate solution (30 ml) was added and the product extracted with dichloromethane (3×30 ml). The organic residues were concentrated and the residue purified using flash column chromatography eluting with ethyl acetate, followed by 2M NH3/MeOH (3-5%) in ethyl acetate to give t-butyl {2-[(4-{3-cyano-5-[(ethylamino)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate (508 mg) as a white solid. This was dissolved in methanol (4 ml), a 4M solution of hydrogen chloride in 1,4-dioxan (10 ml, 40 mmol) was added and the solution then stirred at ambient temperature for 2 hours. The solvent was evaporated, methanol (5 ml) was added and the resulting solution was absorbed onto an SCX-2 column, which was washed with methanol (2 column volumes) and then eluted with a 2M solution of ammonia in methanol (2 column volumes) to give the product as a foam. This was re-precipitated by stirring in diethyl ether (20 ml) to give the title compound as a white solid (359 mg, 53%); NMR Spectrum: (DMSO-d6 373K) 1.08 (t, 3H), 2.62 (q, 2H), 3.67 (s, 2H), 4.73 (br s, 2H), 6.63 (m, 1H), 6.82 (m, 1H), 6.98 (m, 1H), 7.27 (m, 1H), 7.99 (d, 2H), 8.13 (d, 2H), 8.28 (d, 1H), 8.88 (d, 1H), 9.50 (br s, 1H); Mass Spectrum: M+H+ 372.

Workup

  1. stirringthe mixture stirred for a further 30 minutes
  2. extractionthe product extracted with dichloromethane (3×30 ml)
  3. concentrationThe organic residues were concentrated
  4. customthe residue purified
  5. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-841bba784a644299b9bc736d60ee8c85
Source dataset
uspto-grants-2011_03
Patent number
US07897778B2

Reaction notes

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