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

HRID 1686992Notes

Reaction equation

HRID 1686992 reaction equation
[CH3:1][S:2]([N:5]1[CH2:15][CH:14]2[CH2:16][CH:7]([C:8]3[CH:9]=[CH:10][C:11]([NH2:17])=[CH:12][C:13]=32)[CH2:6]1)(=[O:4])=[O:3].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.C(O)(C)C.C(=O)(O)[O-].[Na+]>>[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]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6]2)=[N:20][CH:21]=1

Participants

5

Reactant 4

HCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 6726448610-Methanesulfonyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamine

Product 1

HCID 66829633[5-Chloro-2-(10-methanesulfonyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 31.1%

Conditions

Temperature
130 °C

Procedure

Into a microwave tube was dissolved 10-methanesulfonyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamine (50 mg, 0.2 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (58.0 mg, 0.194 mmol) in isopropyl alcohol (1 mL, 10 mmol). The tube was heated in the microwave at 130° C. for 20 minutes. The reaction solution was poured into saturated sodium bicarbonate solution and was extracted with methylene chloride (6×20 ml). The reaction was dried over magnesium sulfate filtered and was rotovaped to a clear oil. The crude product was chromatographed on silica gel (12 g Isco column) and eluted with a gradient of 0-15% methanol in methylene chloride to yield -[5-Chloro-2-(10-methanesulfonyl-10-aza-tricyclo[6.3.1.0*2,7*]dodeca-2,4,6-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (31.0 mg, 31%) as a white powder. MP: 163.5-165.0° C.; 1H-NMR (CDCl3) δ 10.97 (s, 1H), 8.45 (d, J=8.3 Hz, 1H), 8.03 (s, 1H), 7.65 (s, 1H), 7.55-7.42 (m, 2H), 7.21-7.09 (m, 3H), 6.40 (br s, 1H), 3.40-3.28 (m, 3H), 3.18 (br s, 1H) 3.10 (br s, 1H), 3.02 (dd, J=5.05, 3H), 2.42-2.30 (m, 1H), 2.08-2.00 (m, 1H), 1.90 (s, 3H), 1.81 (d, J=10.9 Hz, 1H), 1.32-1.21 (m, 2H), 0.90-0.81 (m, 2H).

Workup

  1. extractionwas extracted with methylene chloride (6×20 ml)
  2. dry with materialThe reaction was dried over magnesium sulfate
  3. filtrationfiltered
  4. customThe crude product was chromatographed on silica gel (12 g Isco column)
  5. washeluted with a gradient of 0-15% methanol in methylene chloride

Sources & evidence

ORD record
ord-fd5f212892474a858646143e0936cd25
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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