Isopropyl iodide → 2-Cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid (4-benzyl-1-isopropylpiperidin-4-yl)amide

HRID 645503Notes

Reaction equation

HRID 645503 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([NH:14][C:15]([C:17]2[C:18]([NH:25][CH2:26][CH:27]3[CH2:34][CH2:33][C:30]4([CH2:32][CH2:31]4)[CH2:29][CH2:28]3)=[N:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=2)=[O:16])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+].[CH:55](I)([CH3:57])[CH3:56]>C(Cl)Cl.CCOC(C)=O>[CH2:35]([C:11]1([NH:14][C:15]([C:17]2[C:18]([NH:25][CH2:26][CH:27]3[CH2:34][CH2:33][C:30]4([CH2:31][CH2:32]4)[CH2:29][CH2:28]3)=[N:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=2)=[O:16])[CH2:12][CH2:13][N:8]([CH:55]([CH3:57])[CH3:56])[CH2:9][CH2:10]1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 6362Isopropyl iodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 687064324-Benzyl-4-({2-cyano-4-[(spiro[2.5]oct-6-ylmethyl)-amino]-pyrimidine-5-carbonyl}amino)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866277952-Cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid (4-benzyl-1-isopropylpiperidin-4-yl)amide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-benzyl-4-({2-cyano-4-[(spiro[2.5]oct-6-ylmethyl)amino]-pyrimidine-5-carbonyl}amino)piperidine-1-carboxylic acid tert-butyl ester (0.14 mmol) in CH2Cl2 (1.5 mL) is added TFA (0.4 mL) at 0° C. After stirring at room temperature for 0.5 h, the reaction mixture is concentrated in vacuo. The residue is dissolved in DMF (1.5 mL) and treated with K2CO3 (0.35 mmol) and isopropyl iodide (0.28 mmol) at 0° C. After stirring at room temperature for 5 h, the reaction mixture is diluted with AcOEt and washed with H2O and brine. The organic layer is dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by RP-HPLC to give the title compound; 1H NMR (CDCl3), δ: 0.18-0.26 (2H, m), 0.27-0.34 (2H, m), 0.91-0.99 (2H, m), 1.01-1.13 (6H, s), 1.17-1.33 (2H, m), 1.63-1.97 (7H, m), 2.15-2.40 (4H, m), 2.64-2.90 (3H, m), 3.15 (2H, s), 3.46 (2H, dd), 5.28 (1H, s), 7.02-7.10 (2H, m), 7.20-7.30 (3H, m), 8.05 (1H, s), 8.70 (1H, bs).

Workup

  1. concentrationthe reaction mixture is concentrated in vacuo
  2. dissolutionThe residue is dissolved in DMF (1.5 mL)
  3. stirringAfter stirring at room temperature for 5 h
  4. washwashed with H2O and brine
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by RP-HPLC

Sources & evidence

ORD record
ord-3f2d284be33542c78735400454d8edb2
Source dataset
uspto-grants-2010_04
Patent number
US07704996B2

Reaction notes

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