Formaldehyde → HCID 44587366, compound

HRID 645518Notes

Reaction equation

HRID 645518 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[C:12]([O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[N:13][C:14]([C:27]#[N:28])=[N:15][C:16]=1[NH:17][CH2:18][CH:19]1[CH2:26][CH2:25][C:22]2([CH2:24][CH2:23]2)[CH2:21][CH2:20]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[BH3-][C:41]#N.[Na+]>C1COCC1>[CH2:1]([NH:8][C:9]([C:11]1[C:12]([O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:41])[CH2:34][CH2:33]2)=[N:13][C:14]([C:27]#[N:28])=[N:15][C:16]=1[NH:17][CH2:18][CH:19]1[CH2:20][CH2:21][C:22]2([CH2:23][CH2:24]2)[CH2:25][CH2:26]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68708606HCID 68708606, compound

Product 1

HCID 44587366HCID 44587366, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-cyano-4-(2-piperidin-4-yl-ethoxy)-6-[(spiro[2.5]oct-6-ylmethyl)amino]-pyrimidine-5-carboxylic acid benzylamide (0.19 mmol) in THF (2 mL) is added formaldehyde solution (100 μL), and the resulting solution is stirred for 0.5 h at room temperature. After cooled to 0° C., 1 M NaBH3CN solution in THF is added dropwise, and the reaction mixture is stirred for 2 h at room temperature. The reaction is quenched by the addition of H2O, and extracted twice with AcOEt. The organic layer is dried over Na2SO4, filtered, and concentrated. The residue is purified by silica gel column to give 2-cyano-4-[2-(1-methylpiperidin-4-yl)ethoxy]-6-[(spiro[2.5]oct-6-ylmethyl)amino]pyrimidine-5-carboxylic acid benzylamide as a colorless oil; 1H-NMR (CDCl3), δ 0.17-0.30 (4H, m), 0.89-0.94 (2H, m), 1.14-1.29 (3H, m), 1.40-1.50 (2H, m), 1.58-1.78 (9H, m), 1.95-2.01 (3H, m), 2.38 (3H, s), 2.95-2.98 (2H, m), 3.42 (2H, t), 4.46 (2H, t), 4.56 (2H, d), 7.31-7.39 (5H, m), 8.13 (1H, t), 10.16 (1H, t).

Workup

  1. temperatureAfter cooled to 0° C.
  2. stirringthe reaction mixture is stirred for 2 h at room temperature
  3. customThe reaction is quenched by the addition of H2O
  4. extractionextracted twice with AcOEt
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel column

Sources & evidence

ORD record
ord-51b0533e64184cd6a15288601653e68c
Source dataset
uspto-grants-2010_04
Patent number
US07704996B2

Reaction notes

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