Triethylamine → HCID 178496598, compound

HRID 2428049Notes

Reaction equation

HRID 2428049 reaction equation
[NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[C:7]([C:10]3[N:18]=[C:17]4[C:13]([NH:14][C:15](=[O:27])[N:16]4[C@H:19]4[CH2:24][CH2:23][C@@H:22]([O:25][CH3:26])[CH2:21][CH2:20]4)=[C:12]([C:28]([NH2:30])=[O:29])[N:11]=3)[CH:8]=2)[N:3]=[CH:2]1.N/C(/C#N)=C(\NC(N[C@H:40]1[CH2:45][CH2:44][C@@H:43]([O:46][CH3:47])CC1)=O)/C#N.O1CCCCC1N1C2C(=NC=C(C=O)C=2)N=C1.C(N(CC)CC)C>CO>[CH3:26][O:25][C@@H:22]1[CH2:21][CH2:20][C@H:19]([N:16]2[C:15](=[O:27])[NH:14][C:13]3[C:17]2=[N:18][C:10]([C:7]2[CH:8]=[C:9]4[N:1]([CH:43]5[CH2:44][CH2:45][CH2:40][CH2:47][O:46]5)[CH:2]=[N:3][C:4]4=[N:5][CH:6]=2)=[N:11][C:12]=3[C:28]([NH2:30])=[O:29])[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 57474749HCID 57474749, compoundHCID 178496599HCID 178496599, compoundHCID 178496619HCID 178496619, compound

Product 1

HCID 178496598HCID 178496598, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(1H-Imidazo[4,5-b]pyridin-6-yl)-9-(cis-4-methoxycyclohexyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide. 1-((Z)-2-Amino-1,2-dicyanovinyl)-3-(cis-4-methoxycyclohexyl)urea (See example 160.B) (375 mg, 1.42 mmol), 1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-b]pyridine-6-carbaldehyde (See example 130.C) (644 mg, 2.80 mmol), triethylamine (0.4 mL, 2.80 mmol) and methanol (20 mL) were reacted according to General Procedure B. The solution was allowed to stir at room temperature overnight and the resulting precipitate was collected by filtration to give 9-(cis-4-methoxycyclohexyl)-8-oxo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-8,9-dihydro-7H-purine-6-carboxamide. This THP-protected intermediate (235 mg, 0.48 mmol) was dissolved in dioxane (2 mL) and a 4.0 M HCl/dioxane solution (4.0 mL) and water (0.3 mL) were added. The resulting solution was stirred at room temperature overnight. The reaction was neutralized with saturated sodium bicarbonate, extracted with EtOAc (3×50 mL), and pooled organics were dried over sodium sulfate. The crude product was purified via reverse-phase semi-prepatory HPLC (20-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The volatiles were removed under reduced pressure, treated with saturated sodium bicarbonate and extracted with ethyl acetate (3×75 mL). Organic layers were pooled, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting solid was washed with diethyl ether and dried in a vacuum oven at 60° C. overnight to afford the title compound (15 mg, 0.036 mmol, 7.5%) as a white solid. 1H NMR (400 MHz, MeOD-d3) δ 9.56 (s, 1H), 8.50 (m, 1H), 7.80 (m, 1H), 4.31 (m, 1H), 3.51 (m, 1H), 3.39 (s, 3H), 2.77 (m, 2H), 2.07 (m, 4H), 1.53 (m, 4H); MS (ESI) m/z 409.0 [M+1]+; mp 360° C. dec.

Workup

  1. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-a3575d0232794ce3a50c21fef6498d29
Source dataset
uspto-grants-2011_06
Patent number
US07968556B2

Reaction notes

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