Methylamine → HCID 68705300, compound

HRID 645514Notes

Reaction equation

HRID 645514 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:17]2[C:22]([C:23]([OH:25])=O)=[C:21]([NH:26][CH2:27][CH:28]3[CH2:36][CH2:35][C:31]4([CH2:34][CH2:33][CH2:32]4)[CH2:30][CH2:29]3)[N:20]=[C:19]([C:37]#[N:38])[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN.C[CH2:42][N:43]=C=NCCCN(C)C.Cl>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:17]2[C:22]([C:23](=[O:25])[NH:43][CH3:42])=[C:21]([NH:26][CH2:27][CH:28]3[CH2:36][CH2:35][C:31]4([CH2:32][CH2:33][CH2:34]4)[CH2:30][CH2:29]3)[N:20]=[C:19]([C:37]#[N:38])[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68709776HCID 68709776, compound

Product 1

HCID 68705300HCID 68705300, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4[2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy]-2-cyano-6-[(spiro[3.5]non-7-ylmethyl)amino]pyrimidine-5-carboxylic acid (0.23 mmol, step 75.4) and 2 M methyl amine solution (0.30 mmol) in DMF (1 mL) are added EDCI-HCl (0.34 mmol) and HoAt (0.34 mmol) at 0° C. The reaction mixture is stirred at room temperature for 1 h. After dilution with AcOEt, the mixture is washed with H2O and brine. The organic layer is dried over MgSO4, filtered, and concentrated. The residue is purified by silicagel column chromatography to give 4-(2-{2-cyano-5-methylcarbamoyl-6-[(spiro[3.5]non-7-ylmethyl)amino]-pyrimidin-4-yloxy}ethyl)piperidine-1-carboxylic acid tert-butyl ester as a white solid; 1H-NMR (CDCl3), δ: 0.98-1.07 (2H, m), 1.14-1.85 (2H, m), 1.46 (9H, s), 2.70 (2H, t), 2.93 (3H, d), 3.33 (2H, t), 4.05-4.15 (2H, m), 4.54 (2H, t), 7.80-7.85 (1H, m), 10.10-10.15 (1H, m).

Workup

  1. washAfter dilution with AcOEt, the mixture is washed with H2O and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by silicagel column chromatography

Sources & evidence

ORD record
ord-99c4c9dda4d049908ba15bd020d20f67
Source dataset
uspto-grants-2010_04
Patent number
US07704996B2

Reaction notes

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