Hydrochloric Acid → 6-Chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-amine Dihydrochloride

HRID 541750Notes

Reaction equation

HRID 541750 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([Cl:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=2)=[CH:11][C:10]=1[CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([NH:32]C(=O)OC(C)(C)C)[CH:29]=[CH:30][CH:31]=1)=O)(C)(C)C.[ClH:40].O1CCOCC1>C(#N)C.O.CC(O)CC>[ClH:22].[ClH:40].[Cl:22][C:21]1[CH:20]=[N:19][C:18]2[NH:32][C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([CH:27]=3)[CH2:25][CH2:24][C:10]3[CH:11]=[C:12]([NH:15][C:16]=1[N:17]=2)[CH:13]=[CH:14][C:9]=3[NH2:8]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 57962263tert-Butyl [3-(2-{2-[(tert-butoxycarbonyl)amino]-5-[(2,5-dichloropyrimidin-4-yl)amino]phenyl}ethyl)phenyl]carbamate

Product 1

HCID 668960506-Chloro-2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-amine DihydrochlorideYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6568(+-)-2-ButanolSolvent

Procedure

A solution of tert-butyl [3-(2-{2-[(tert-butoxycarbonyl)amino]-5-[(2,5-dichloropyrimidin-4-yl)amino]phenyl}ethyl)phenyl]carbamate (4.70 g, 8.18 mmol) in acetonitrile (750 mL), water (75 mL) and 2-butanol (1.0 mL) was treated with 4.0 M of hydrogen chloride in 1,4-dioxane (7.2 mL, 28.6 mmol) and refluxed for 20 hours. The reaction mixture was concentrated and the tan solid was triturated with dichloromethane and methanol to give the desired product (2.83 g, 84%). LCMS calculated for C18H17ClN5(M+H)+: m/z=338.1. 1H NMR (400 MHz, DMSO-d6): δ 8.37 (s, 1H), 7.89 (s, 1H), 7.79 (s, 1H), 7.59 (m, 1H), 7.43 (m, 3H), 7.36 (d, 1H), 7.17 (m, 2H), 6.91 (dd, 2H), 3.08 (d, 4H).

Workup

  1. temperaturerefluxed for 20 hours
  2. concentrationThe reaction mixture was concentrated
  3. customthe tan solid was triturated with dichloromethane and methanol

Sources & evidence

ORD record
ord-936308a146e140a19aa23433aac4f109
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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