Hydrochloric Acid → 2-[5-Chloro-2-(10-(2-methoxy-ethyl)-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1686987Notes

Reaction equation

HRID 1686987 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:15][CH:14]2[CH2:16][CH:7]([C:8]3[C:13]2=[CH:12][C:11]([NH2:17])=[CH:10][CH:9]=3)[CH2:6]1.Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=2[C:28]([NH:30][CH3:31])=[O:29])[C:22]([Cl:36])=[CH:21][N:20]=1.Cl.O1CCOCC1.[Na]>O>[Cl:36][C:22]1[C:23]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=2[C:28]([NH:30][CH3:31])=[O:29])=[N:24][C:19]([NH:17][C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[CH:7]2[CH2:16][CH:14]3[CH2:15][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:6]2)=[N:20][CH:21]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 5360545SodiumHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 6726456610-(2-Methoxy-ethyl)-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamine

Product 1

HCID 668295482-[5-Chloro-2-(10-(2-methoxy-ethyl)-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 46.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

10-(2-Methoxy-ethyl)-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamine (45 mg, 0.19 mmol), 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (58 mg, 0.19 mmol) and 4N HCl in dioxane (53 μl, 0.21 mmol) were combined in a microwave tube. The reaction was heated to at 120° C. for 40 minutes in the microwave. The reaction was poured into water (50 ml) and saturated sodium bicarb (90 ml) and extracted 3 times with 25 ml portions of methylene chloride. The combined organic was dried over magnesium sulfate, filtered and evaporated to a brown oil. The crude reaction was purified on a 12 g Isco silica gel column using 0-15% methanol in methylene chloride as the eluent to yield 2-[5-Chloro-2-(10-(2-methoxy-ethyl)-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (43.6 mg, 43%) as a yellow foam. MP: 104.5-105.5° C.; 1H-NMR (CDCl3) δ 9.68 (d, J=7.8 Hz, 1H), 8.12 (s, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.42 (m, 2H), 7.21 (s, 1H), 7.08 (d, J=8.1 Hz, 2H), 6.91 (s, 1H), 6.20 (br s, 1H), 3.33 (t, J=5.8 Hz, 2H), 3.20 (s, 3H), 3.11-2.98 (m, 6H), 2.86 (br s, 2H), 2.59-2.46 (m, 4H), 2.39 (m, 1H), 1.73 (d, J=10.36, 1H); LC/MS (ESI+): 493 (M+H).

Workup

  1. extractionextracted 3 times with 25 ml portions of methylene chloride
  2. dry with materialThe combined organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated to a brown oil
  5. customThe crude reaction
  6. customwas purified on a 12 g Isco silica gel column

Sources & evidence

ORD record
ord-84de20eaf6ba4c5ab60224315e4b2846
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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