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

HRID 1040676Notes

Reaction equation

HRID 1040676 reaction equation
[CH:1]([N:4]1[CH2:14][CH:13]2[CH2:15][CH:6]([C:7]3[C:12]2=[CH:11][C:10]([NH2:16])=[CH:9][CH:8]=3)[CH2:5]1)([CH3:3])[CH3:2].Cl[C:18]1[N:23]=[C:22]([NH:24][C:25]2[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=2[C:27]([NH:29][CH3:30])=[O:28])[C:21]([Cl:35])=[CH:20][N:19]=1.Cl.O1CCOCC1.[Na]>O>[Cl:35][C:21]1[C:22]([NH:24][C:25]2[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=2[C:27]([NH:29][CH3:30])=[O:28])=[N:23][C:18]([NH:16][C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[CH:6]2[CH2:15][CH:13]3[CH2:14][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5]2)=[N:19][CH:20]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 5360545SodiumHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 6726347010-Isopropy-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamine

Product 1

HCID 668294922-[5-chloro-2-(10-isopropyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 35%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

10-Isopropy-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamine (30 mg, 0.14 mmol), 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (41 mg, 0.14 mmol) and 4N HCl in dioxane (28 μl, 0.15 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 8 g Isco basic alumina column using 0-2% methanol in methylene chloride as the eluent to yield 2-[5-chloro-2-(10-isopropyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (23.2 mg, 35%) as a red orange foam. 1H-NMR (CDCl3) δ 11.0 (s, 1H), 8.68 (d, J=8.3 Hz, 1H), 8.08 (s, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.40 (t, J=7.3 Hz, 1H), 7.37 (s, 1H), 7.21 (s, 1H), 7.06 (dd, J=3.3, 6.8 Hz, 2H), 3.10-3.0 (m, 4H), 2.75 (m, 2H), 2.55 (m, 4H), 2.27 (m, 1H), 1.68 (d, J=10.1 Hz, 1H), 0.85 (d, J=6.6 Hz, 6H); LC/MS (ESI+): 477 (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 8 g Isco basic alumina column

Sources & evidence

ORD record
ord-6af8a61e0f6d49fe8c77443b09b02b98
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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