Hydrochloric Acid → HCID 66829403, compound

HRID 1040757Notes

Reaction equation

HRID 1040757 reaction equation
[CH2:1]([N:3]1[CH2:13][CH:12]2[CH2:14][CH2:15][CH:5]([C:6]3[CH:7]=[CH:8][C:9]([NH2:16])=[CH:10][C:11]=32)[CH2:4]1)[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>CC(O)C>[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:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[CH:5]2[CH2:15][CH2:14][CH:12]3[CH2:13][N:3]([CH2:1][CH3:2])[CH2:4]2)=[N:19][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 67263683HCID 67263683, compound

Product 1

HCID 66829403HCID 66829403, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

10-Ethyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2(7),3,5-trien-4-ylamine (29.8 mg, 0.138 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (45 mg, 0.152 mmol, 1.1 eq) were dissolved in IPA (1.5 mL). 4.0 M HCl in dioxane (38 μL, 0.152 mmol, 1.1 eq) was added and the reaction was heated at 130° C. in a microwave for 10 minutes. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (10 mL) and washed with sat. NaHCO3 (10 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-5% MeOH/CH2Cl2 as the eluting solvent to obtain 2-[5-chloro-2-(10-ethyl-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as a yellow solid (38 mg, 58%). m.p. dec. at 106° C.; LCMS (m/e) 477 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 11.02 (s, 1H), 8.67 (d, 1H, J=8.4 Hz), 8.09 (s, 1H), 7.50-7.40 (m, 2H), 7.34 (d, 1H, J=2.3 Hz), 7.30-7.20 (m, 1H), 7.02 (t, 1H, J=7.6 Hz), 7.00 (d, 1H, J=7.9 Hz), 6.87 (s, 1H), 6.19 (bs, 1H), 3.03 (d, 3H, 4.9 Hz), 3.00-2.90 (m, 4H), 2.44 (q, 2H, J=7.1 Hz), 2.21-2.16 (m, 4H), 1.64-1.60 (m, 2H), 1.00 (t, 3H, J=7.1 Hz).

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (10 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by basic alumina chromatography

Sources & evidence

ORD record
ord-f306aab34e5944e68032928a8efff8d0
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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