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Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-N,3-dimethylbenzamide

HRID 1041780
Notes
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Reaction equation

HRID 1041780 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[C:6]([CH3:13])([CH3:12])[NH:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[NH2:7][C:8](=[O:11])[CH2:9][CH2:10][C:4]1[CH:3]=[C:2]([NH:1][C:17]2[N:22]=[C:21]([NH:23][C:24]3[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:25]=3[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=2)[CH:15]=[CH:14][C:5]=1[C:6]([CH3:13])=[CH2:12]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 672644267-Amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-oneHCID 866338742-(2,5-dichloropyrimidin-4-ylamino)-N,3-dimethylbenzamide

Product 1

HCID 672641682-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-N,3-dimethylbenzamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A suspension of 7-amino-1,1-dimethyl-1,2,4,5-tetrahydrobenzo[c]azepin-3-one (46 mg), 2-(2,5-dichloropyrimidin-4-ylamino)-N,3-dimethylbenzamide (42 mg), and camphorsulfonic acid (40 μL of a 100 mg/mL aqueous solution) were heated in isopropanol (2 mL) for 4 hours at 120° C. using microwave irradiation. The solvent was evaporated to afford crude 2-(2-(3-(3-amino-3-oxopropyl)-4-(prop-1-en-2-yl)phenylamino)-5-chloropyrimidin-4-ylamino)-N,3-dimethylbenzamide. The crude mixture was dissolved in TFA and allowed to stand for 4 hours, then concentrated. Purification by semi-preparative HPLC provided 2-(5-chloro-2-(1,1-dimethyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-ylamino)pyrimidin-4-ylamino)-N,3-dimethylbenzamide as the TFA salt. The non-salt was obtained by stirring the TFA salt in acetonitrile with 300 mg of MP-carbonate (Argonaut, 2.91 mmol/g) for 2 days. The resin was separated by filtration, then washed with methanol and methylene chloride. The filtrate was concentrated and the residue triturated with ethyl ether to provide 14 mg of the neutral compound: 1H NMR (300 MHz, CDCl3 with 5% CD3OD) δ 8.05 (s, 1H), 7.5-7.4 (m, 2H), 7.35 (dd, 1H), 7.3 (d, 1H), 7.15 (d, 1H), 7.1 (dd, 1H), 2.9 (s, 3H), 2.8 (m, 2H), 2.6 (m, 2H), 2.3 (s, 3H) 1.8 (s, 6H).

Workup

  1. custommicrowave irradiation
  2. customThe solvent was evaporated

Sources & evidence

ORD record
ord-57e907881a1e4c57b862266281bc94be
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08552186B2

Reaction notes

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