Hydrochloric Acid → HCID 59240648, compound

HRID 42191

Reaction equation

HRID 42191 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[N:10]([C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][N:12]=2)[CH2:9][CH2:8][N:7]([C:25](OC(C)(C)C)=O)[CH2:6]1)=[O:4].Cl.[CH2:33]([C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)C(Cl)=[N:42][N:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH2:51](N(CC)CC)C>C(OCC)C.C(Cl)Cl>[CH2:24]([O:23][C:21]([C:14]1[C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]([N:10]2[CH2:9][CH2:8][N:7]([C:25]3[C:48]4[C:49](=[CH:44][CH:45]=[CH:46][CH:47]=4)[C:40]([CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[N:41][N:42]=3)[CH2:6][C@H:5]2[C:3]([O:2][CH3:1])=[O:4])=[N:12][CH:13]=1)=[O:22])[CH3:51]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 64045661-Benzyl-4-chlorophthalazineHCID 68707290(S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester

Product 1

HCID 59240648HCID 59240648, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a methylene chloride (0.02M) solution of (S)-4-(5-Methoxycarbonyl-4-trifluoromethyl-pyrimidin-2-yl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl-ester (69 mg, 0.153 mmol), is added 1N HCl (2 mmol), 2M in diethyl ether. Stir reaction mixture at room temperature for 18 h. Concentrate and dilute with dioxane (0.1 M), followed by addition of 1-benzyl-4-chloro-phthalazine (0.153 mmol) and triethylamine (0.459 mmol). Microwave reaction mixture for 30 min at 150° C. MS shows some starting material still present. Microwave for an additional 2.5 h at 150° C. Concentrate reaction mixture and purify by column chromatography 0-75% ethyl acetate/heptane gradient to afford the title compound. (8% yield)

Workup

  1. customreaction mixture at room temperature for 18 h
  2. concentrationConcentrate
  3. additiondilute with dioxane (0.1 M)
  4. customMicrowave reaction mixture for 30 min at 150° C
  5. concentrationConcentrate
  6. customreaction mixture
  7. custompurify by column chromatography 0-75% ethyl acetate/heptane gradient

Sources & evidence

ORD record
ord-1fb9fdad713d49a7b704ceef49f7cac2
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Linked notes

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