1-Hydroxybenzotriazole → 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-5-(1H-imidazol-1-yl)pentan-1-one

HRID 870578Notes

Reaction equation

HRID 870578 reaction equation
Cl.CN(C)CCCN=C=NCC.[CH2:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH:14]1[NH:22][C:23]1[N:24]=[CH:25][C:26]2[CH2:32][NH:31][CH2:30][CH2:29][C:27]=2[N:28]=1.[N:33]1([CH2:38][CH2:39][CH2:40][CH2:41][C:42](O)=[O:43])[CH:37]=[CH:36][N:35]=[CH:34]1.ON1C2C=CC=CC=2N=N1>ClCCl.C(N(CC)CC)C>[CH2:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH:14]1[NH:22][C:23]1[N:24]=[CH:25][C:26]2[CH2:32][N:31]([C:42](=[O:43])[CH2:41][CH2:40][CH2:39][CH2:38][N:33]3[CH:37]=[CH:36][N:35]=[CH:34]3)[CH2:30][CH2:29][C:27]=2[N:28]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 128033135-(1H-imidazol-1-yl)pentanoic acidHCID 86726522N-(indan-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 867265391-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-5-(1H-imidazol-1-yl)pentan-1-oneYield 45%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.288 g; 2.0 equiv; 1.50 mmoles) to a solution of N-indan-2-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine (0.20 m; 1.0 equiv; 0.75 mmoles), 5-imidazol-1-ylpentanoic acid (0.152 g; 1.2 equiv; 0.90 mmoles), and 1-hydroxybenzotriazole (0.203 g; 2.0 equiv; 1.50 mmoles) in dichloromethane (20 mL) and triethylamine (0.52 mL). Stir the mixture for 18 hours, then concentrate, add water (10 mL), and extract with ethyl acetate (3×20 mL). Dry the combined organic extracts over anhydrous sodium sulfate, filter, and concentrate. Purify the crude product by column chromatography (0 to 10% methanol in dichloromethane) to afford 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-5-(1H-imidazol-1-yl)pentan-1-one (0.14 g; 45%) as a colorless oil: MS (m/z): 417 (M+1).

Workup

  1. concentrationconcentrate
  2. additionadd water (10 mL)
  3. extractionextract with ethyl acetate (3×20 mL)
  4. dry with materialDry the combined organic extracts over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude product by column chromatography (0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2178341f785a4c62b52238325137c89b
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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