Hydrochloric Acid → HCID 178422911, compound

HRID 1042274Notes

Reaction equation

HRID 1042274 reaction equation
COC1C=CC(C[N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[C:17]2[C:18]([NH:23][C:24]3[C:33]([CH3:34])=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=[CH:27][N:28]=[C:29]4[NH:35][C:36]3[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)=CC=1.Cl.CO>C(O)(C(F)(F)F)=O.CC#N.CCOCC.C(Cl)Cl>[N:12]1[C:13]([C:17]2[C:18]([NH:23][C:24]3[C:33]([CH3:34])=[CH:32][CH:31]=[C:30]4[C:25]=3[CH:26]=[CH:27][N:28]=[C:29]4[NH:35][C:36]3[CH:37]=[CH:38][C:39]([C:40]#[N:41])=[CH:42][CH:43]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)=[C:14]2[C:9]([NH:8][CH:16]=[N:15]2)=[N:10][CH:11]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 687244614-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

Product 1

HCID 178422911HCID 178422911, compoundYield 43.3%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-(5-(3-(9-(4-methoxybenzyl)-9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile (0.37 g, 0.63 mmol) in TFA (3 mL) was stirred in a 65° C. oil bath for 4.5 h. The reaction mixture was concentrated to give a dark orange residue. The residue was dissolved in MeCN (4 mL) and added dropwise to 1 N HCl in Et2O (100 mL). The resulting precipitate was collected by suction filtration. The bright yellow solid was dissolved in MeOH (50 mL) and 2M NH3 in MeOH (50 mL) and adsorbed onto a pad of silica gel. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with a gradient of 1% to 10% 1 M NH3.MeOH in CH2Cl2 (over 30 min), to provide 4-(5-(3-(9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile (0.128 g, 43% yield). The orange solid was suspended in MeOH (5 mL), Et2O (100 mL), and hexane (100 mL), and stirred at reflux for 2 h. The solid was collected by suction filtration, washed with hexane and dried in vacuo at 80° C. overnight to give 4-(5-(3-(9H-purin-6-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile as an amorphous orange solid. 1H NMR (400 MHz, DMSO-d6) □ ppm 2.38 (s, 3H), 6.91 (dd, J=7.78, 4.77 Hz, 1H), 7.28 (d, J=5.52 Hz, 1H), 7.66 (d, J=8.53 Hz, 1H), 7.75 (d, J=8.53 Hz, 2H), 8.01 (d, J=5.52 Hz, 1H), 8.03-8.07 (m, 1H), 8.13 (d, J=8.53 Hz, 2H), 8.42 (d, J=9.03 Hz, 1H), 8.74 (s, 1H), 9.06 (s, 1H), 9.66 (s, 1H), 9.71-9.85 (m, 1H), 11.87 (s, 1H), 13.84 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a dark orange residue
  3. filtrationThe resulting precipitate was collected by suction filtration
  4. dissolutionThe bright yellow solid was dissolved in MeOH (50 mL)
  5. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  6. washeluting with a gradient of 1% to 10% 1 M NH3

Sources & evidence

ORD record
ord-82d49d1f55014b1e9c5d3817861a1097
Source dataset
uspto-grants-2013_10
Patent number
US08557830B2

Reaction notes

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