3-Pyridinemethanamine → HCID 22744293, compound

HRID 47872Notes

Reaction equation

HRID 47872 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[N:7]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[C:8]([CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:9]2)=[CH:4][C:3]=1[CH2:25][N:26]([C:30]1[CH:42]=[CH:41][C:33]([C:34]([O:36]C(C)(C)C)=O)=[CH:32][CH:31]=1)[CH2:27][C:28]#[CH:29].[NH2:43][CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl.FC(F)(F)C(O)=O.CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[N:7]([CH2:19][CH2:20][N:21]([CH3:22])[CH3:23])[C:8]([CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:9]2)=[CH:4][C:3]=1[CH2:25][N:26]([C:30]1[CH:42]=[CH:41][C:33]([C:34]([NH:43][CH2:44][C:45]2[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=2)=[O:36])=[CH:32][CH:31]=1)[CH2:27][C:28]#[CH:29]

Participants

8

Reactant 4

HCID 310183-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 22744279HCID 22744279, compound

Product 1

HCID 22744293HCID 22744293, compoundYield 24.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 4-[N-[7-chloro-3-(2-dimethylaminoethyl)-4-oxo-2-piperidin-1-ylmethyl-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.100 g, 0.17 mmol) (Preparation Example 32) in dichloromethane (2.5 ml) and trifluoroacetic acid (3.5 ml) was stirred at room temperature for 55 min with protection from the light. The solvent was then removed in vacuo and the residue was triturated with ether and dried in vacuo over P2O5. This solid was dissolved in anhydrous DMF (5 ml) under argon and the solution was placed in an ice-bath. A solution of 3-(aminomethyl)pyridine (0.027 g, 0.25 mmol) in DMF (0.2 nil) was then added followed by PyBOP® (0.092 g, 0.37 mmol) and diisopropylethylamine (0.197 g, 1.53 mmol). Stirring was continued at 0° C. for 15 min; then the ice-bath was removed and the reaction mixture was stirred for an additional 4 h at room temperature. The solvent was then removed in vacuo and the residue was chromatographed on aluminium oxide 90 active (neutral) column eluting first with chloroform and then with 1% methanol in chloroform. The product was obtained as a white solid (0.026 g, 24%), mp 90-93° C.; 1H-NMR (DMSO-d6) 1.40-1.49 (m, 6H, piperidine CH2CH2CH2), 2.20 (s, 6H, Me2N) 2.41 (m, 4H, piperidine CH2NCH2), 2.55 (t (obscured), 2H, Me2NCH2), 3.21(s, 1H, C≡CH), 3.62 (s, 2H, 2-CH2), 4.25 (t, J=7.0 Hz, 2H, N3-CH2), 4.38 (s, 2H, CH2C≡C), 4.45 (d, J=5.7 Hz, 2H, CONHCH 4.78 (s, 2H, 6-CH2), 6.78 (d, J=8.8 Hz, 2H, 3,5′-ArH), 7.32 (dd, J=4.8, 7.8 Hz, 1H, pyr 5-H), 7.68 (d, J=8.0 Hz, 1H, pyr 4-H), 7.75 (d, J=8.7 Hz, 2H, 2′,6′-ArH), 7.85, 7.91 (2×s, 2H, 5-H, 8-H), 8.43 (d, J=5.1 Hz, 1H, pyr 6-H), 8.52 (s, 1H, pyr 2-H), 8.74 (t, J=5.9 Hz, 1H, CONH).; MS (FAB, m/z) 626, 628 [(M+H)+, 100%, 35% respectively; Cl isotopic pattern]. FAB-HRMS: measured 626.3025; calculated for C35H41ClN7O2 (M+H)+: 626.3010.

Workup

  1. customThe solvent was then removed in vacuo
  2. customthe residue was triturated with ether
  3. dry with materialdried in vacuo over P2O5
  4. dissolutionThis solid was dissolved in anhydrous DMF (5 ml) under argon
  5. customthe solution was placed in an ice-bath
  6. customthen the ice-bath was removed
  7. stirringthe reaction mixture was stirred for an additional 4 h at room temperature
  8. customThe solvent was then removed in vacuo
  9. customthe residue was chromatographed on aluminium oxide 90 active (neutral) column
  10. washeluting first with chloroform

Sources & evidence

ORD record
ord-e10522723a404e24b4bb384ac204b965
Source dataset
uspto-grants-2004_03
Patent number
US06699861B1

Reaction notes

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