4-Aminopyridine → HCID 86726557, compound

HRID 870593Notes

Reaction equation

HRID 870593 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH2:13]([OH:18])[CH2:14][CH2:15][C:16]#[CH:17].[CH2:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH:20]1[NH:28][C:29]1[N:30]=[CH:31][C:32]2[CH2:38][NH:37][CH2:36][CH2:35][C:33]=2[N:34]=1.N1C=CC(N)=CC=1.C(N(CC)CC)C>ClCCl>[CH2:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH:20]1[NH:28][C:29]1[N:30]=[CH:31][C:32]2[CH2:38][N:37]([C:1]([O:18][CH2:13][CH2:14][CH2:15][C:16]#[CH:17])=[O:2])[CH2:36][CH2:35][C:33]=2[N:34]=1

Participants

7

Reactant 5

HCID 17274-AminopyridineHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 793464-Pentyn-1-olHCID 86726522N-(indan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 86726557HCID 86726557, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add 1,1′-carbonyldiimidazole (0.936 g; 5.66 mmoles) slowly dropwise to a −78° C. solution of 4-pentyn-1-ol (0.50 mL; 5.39 mmoles) in dichloromethane (18 mL). Allow the reaction to warm to ambient temperature for 30 minutes, then add half of this solution to a solution of N-indan-2-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (0.581 g; 1.05 equiv; 2.18 mmoles), 4-pyridinamine, N,N-dimethyl-(0.258 g; 1.0 equiv; 2.08 mmoles), and triethylamine (0.58 mL; 2.0 equiv; 4.15 mmoles). Warm the resulting pale yellow solution to ambient temperature and stir for 16 hours, then warm to 40° C. for an additional 24 hours. Cool the reaction mixture to ambient temperature and load directly onto a silica gel column. Purify by column chromatography (20 to 100% ethyl acetate in dichloromethane) to afford pent-4-yn-1-yl 2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (0.76 g; 88%): MS (m/z): 377(M+1).

Workup

  1. customthe reaction
  2. temperatureWarm the resulting pale yellow solution to ambient temperature
  3. temperaturewarm to 40° C. for an additional 24 hours
  4. temperatureCool the reaction mixture to ambient temperature
  5. customPurify by column chromatography (20 to 100% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-94196737fdb9400d90835fa408ba614e
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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