Acetic Acid → HCID 178462791, compound

HRID 1259509Notes

Reaction equation

HRID 1259509 reaction equation
F[C:2](F)(F)[C:3](O)=O.[CH3:8][O:9][C:10]1[C:19]2[N:18]=[C:17]([NH:20][C:21](=[O:28])[C:22]3[CH:27]=[CH:26][CH:25]=[N:24][CH:23]=3)[N:16]3[CH2:29][CH2:30][N:31]=[C:15]3[C:14]=2[CH:13]=[CH:12][C:11]=1[O:32][CH2:33][CH2:34][CH:35]1[O:40][CH2:39][CH2:38][NH:37][CH2:36]1.C(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.Cl>C1COCC1.CO>[CH2:2]([N:37]1[CH2:38][CH2:39][O:40][CH:35]([CH2:34][CH2:33][O:32][C:11]2[CH:12]=[CH:13][C:14]3[C:15]4[N:16]([CH2:29][CH2:30][N:31]=4)[C:17]([NH:20][C:21](=[O:28])[C:22]4[CH:27]=[CH:26][CH:25]=[N:24][CH:23]=4)=[N:18][C:19]=3[C:10]=2[O:9][CH3:8])[CH2:36]1)[CH3:3]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 178493839HCID 178493839, compound

Product 1

HCID 178462791HCID 178462791, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-[7-Methoxy-8-(2-morpholin-2-ylethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide trifluoroacetate (100 mg, 0.18 mol) in THF was treated with acetaldehyde (30 μL, 0.53 mmol) and stirred for 30 min. before adding sodium triacetoxyborohydride (113 mg, 0.53 mmol) and acetic acid (13 μL, 0.23 mmol). The reaction mixture was stirred at 60 C overnight after which it was diluted with methanol and a drop of 2 N hydrochloric acid to dissolve all solids. The crude solution was purified by HPLC (Gilson, 5% MeCN/95% H2O to 50% MeCN/50% H2O gradient, 0.1% TFA). The fractions were concentrated under reduced pressure then diluted with a minimum of methanol and pulled through a silica bound NH2 cartridge to give the title compound as a solid (17 mg, 20%): HPLC MS RT=0.21 min, MH+=479.1; 1H NMR (DMSO-d6) δ: 12.75 (1H, s), 9.32 (1H, s), 8.71 (1H, d), 8.45 (1H, d), 7.59 (1H, d), 7.54-7.47 (1H, m), 7.06 (2H, d), 4.23-4.08 (3H, m), 4.06-3.98 (2H, m) 3.92 (3H, s), 3.77 (1H, d), 3.67-3.57 (1H, m), 3.46 (1H, t), 2.84 (1H, d), 2.68 (1H, d), 2.30 (2H, q), 1.99-1.79 (3H, m), 1.74 (1H, t), 0.99 (3H, t).

Workup

  1. stirringThe reaction mixture was stirred at 60 C overnight after which it
  2. customThe crude solution was purified by HPLC (Gilson, 5% MeCN/95% H2O to 50% MeCN/50% H2O gradient, 0.1% TFA)
  3. concentrationThe fractions were concentrated under reduced pressure
  4. additionthen diluted with a minimum of methanol

Sources & evidence

ORD record
ord-ac03d77f5bf74787bbc9192f0f5fc383
Source dataset
uspto-grants-2013_06
Patent number
US08466283B2

Reaction notes

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