Triethylamine → HCID 178521183, compound

HRID 713516Notes

Reaction equation

HRID 713516 reaction equation
CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[F:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH:33]3[CH2:38][CH2:37][N:36]([CH2:39][C:40](O)=[O:41])[CH2:35][CH2:34]3)=[N:29][NH:30]2)=[CH:26][CH:25]=1.[NH2:43][CH2:44][C:45]1[NH:46][C:47](=[O:55])[C:48]2[CH2:54][O:53][CH2:52][CH2:51][C:49]=2[N:50]=1.CCN(CC)CC>CN(C=O)C.[Cl-].[Na+].O>[F:23][C:24]1[CH:32]=[C:31]2[C:27]([C:28]([CH:33]3[CH2:38][CH2:37][N:36]([CH2:39][C:40]([NH:43][CH2:44][C:45]4[NH:46][C:47](=[O:55])[C:48]5[CH2:54][O:53][CH2:52][CH2:51][C:49]=5[N:50]=4)=[O:41])[CH2:35][CH2:34]3)=[N:29][NH:30]2)=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1357418942-(Aminomethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-oneHCID 178525828HCID 178525828, compound

Product 1

HCID 178521183HCID 178521183, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of EDCl (0.22 g, 1.17 mmol), HOBT (0.16 g, 1.17 mmol) in 10 mL of DMF were added [4-(6-fluoro-1H-indazol-3-yl)-piperidin-1-yl]-acetic acid (0.27 g, 1.0 mmol), 2-aminomethyl-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (0.19 g, 1.1 mmol), and Et3N (0.40 g, 3.9 mmol). The reaction mixture was stirred at ambient temperature for 15 hours then poured into a separatory funnel containing brine. After separation, the aqueous layer was extracted with DCM (50 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution, dried over Na2SO4, filtered and concentrated in vacuo to yield an oily liquid. Purification by flash chromatography gave the title compound (89.0 mg, 0.19 mmol, 20% yield) as a yellow solid. MS (ESI) m/z 440.8 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 0.96 min. 1H NMR (400 MHz, MeOD) δ ppm 1.94-2.27 (m, 4H), 2.36-2.56 (m, 2H), 2.64 (br. s., 2H), 2.98-3.46 (m, 4H), 3.90 (br. s., 2H), 4.27-4.59 (m, 2H), 4.72-5.01 (m, 3H), 6.91 (br. s., 1H), 7.14 (br. s., 1H), 7.82 (br. s., 1H). HRMS calculated for C22H26FN6O3: 441.2050 (M+H). found (ESI, [M+H]+): 441.2067.

Workup

  1. additionthen poured into a separatory funnel
  2. customAfter separation
  3. extractionthe aqueous layer was extracted with DCM (50 mL)
  4. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto yield an oily liquid
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-28442352ff634ca1b2dbcaea7cf139ed
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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