Hydrochloric Acid → (+/-)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1686943Notes

Reaction equation

HRID 1686943 reaction equation
Cl.O1CCOCC1.Cl[C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=2[C:18]([NH:20][CH3:21])=[O:19])[C:12]([Cl:26])=[CH:11][N:10]=1.[CH2:27]([N:29]1[CH:38]2[CH2:39][CH2:40][CH:30]1[C:31]1[CH:32]=[C:33]([NH2:41])[CH:34]=[CH:35][C:36]=1[CH2:37]2)[CH3:28].C(=O)([O-])[O-]>COCCO>[Cl:26][C:12]1[C:13]([NH:15][C:16]2[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=2[C:18]([NH:20][CH3:21])=[O:19])=[N:14][C:9]([NH:41][C:33]2[CH:34]=[CH:35][C:36]3[CH2:37][CH:38]4[N:29]([CH2:27][CH3:28])[CH:30]([CH2:40][CH2:39]4)[C:31]=3[CH:32]=2)=[N:10][CH:11]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 19660Carbonate IonHCID 312751,4-DioxaneHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 67264063(+/-)-12-Ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamine

Product 1

HCID 131729545(+/-)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamideYield 11%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

2-methoxyethanol (8.6 mL), 4N HCl in p-dioxane (0.215 mL, 1.2 eq) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (129 mgs, 1 eq) and (+/−)-12-Ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamine was heated to 120° C. for 2 h. The mixture cooled to room temp treated with 3 equivalents of MP-carbonate and stirred for 30 min. Filtration, followed by concentration and purification by ISCO chromatography (12 gram column, SiO2, gradient 20% EtOAc/hexane to 100% EtOAc) gave (+/−)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (45 mg, 11%). MP: 218-221° C.; 1H-NMR (CDCl3) δ 11.10 (s, 1H), 8.65 (d, J=8.1 Hz, 1H), 8.1 (s, 1H), 7.51-7.47 (m, 2H), 7.28-7.26 (m, 1H), 7.12-7.10 (m, 1H), 7.00 (s, 1H), 6.79 (d, J=7.8 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 6.52-6.49 (m, 1H), 3.89-3.84 (m, 2H), 3.58-3.55 (m, 2H), 3.05-3.03 (m, 1H), 3.04 (d, J=5.1 Hz, 3H), 2.61-2.51 (m, 3H), 2.25-2.21 (m, 2H), 1.18-1.10 (m, 3H); LC/MS (ESI+): 463.34 (M+H).

Workup

  1. filtrationFiltration
  2. concentrationfollowed by concentration and purification by ISCO chromatography (12 gram column, SiO2, gradient 20% EtOAc/hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-52f8de558ec04418afce8b5556e0293f
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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