Propargyl alcohol → 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(prop-2-yn-1-yloxy)propan-1-one

HRID 870580Notes

Reaction equation

HRID 870580 reaction equation
N12CCCN=C1CCCCC2.[CH2:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]1[NH:21][C:22]1[N:23]=[CH:24][C:25]2[CH2:31][N:30]([C:32](=[O:35])[CH:33]=[CH2:34])[CH2:29][CH2:28][C:26]=2[N:27]=1.[CH2:36]([OH:39])[C:37]#[CH:38]>>[CH2:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]1[NH:21][C:22]1[N:23]=[CH:24][C:25]2[CH2:31][N:30]([C:32](=[O:35])[CH2:33][CH2:34][O:39][CH2:36][C:37]#[CH:38])[CH2:29][CH2:28][C:26]=2[N:27]=1

Participants

4

Reactant 3

HCID 7859Propargyl alcoholHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 867265401-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]prop-2-en-1-one

Product 1

HCID 867265411-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(prop-2-yn-1-yloxy)propan-1-oneYield 48%

Conditions

Temperature
50 °C

Procedure

Add 1,8-diazabicyclo [5.4.0]undec-7-ene (0.035 mL; 0.15 equiv; 0.23 mmoles) to a solution of 1-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]prop-2-en-1-one (0.5 g; 1.0 equiv; 1.56 mmoles) and 2-propyn-1-ol (5.0 mL; 55 equiv; 85.86 mmoles). Stir the reaction at ambient temperature for 16 hours, then heat to 50° C. for 36 hours. Concentrate the solution to a brown oil, then purify the crude product by column chromatography (20 to 100% ethyl acetate in dichloromethane) to afford the desired 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(prop-2-yn-1-yloxy)propan-1-one (0.28 g; 48%): MS (m/z): 377 (M+1).

Workup

  1. customthe reaction at ambient temperature for 16 hours
  2. concentrationConcentrate the solution to a brown oil
  3. custompurify the crude product by column chromatography (20 to 100% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-64e1f5b6e6a64552a21de9b16de4843e
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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