Diisopropylethylamine → N-Cyclopropylmethyl-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-N-(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-ylmethyl)-acetamide

HRID 713488Notes

Reaction equation

HRID 713488 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:53]1([CH2:56][NH:57][CH2:58][C:59]2[NH:60][C:61](=[O:69])[C:62]3[CH2:68][O:67][CH2:66][CH2:65][C:63]=3[N:64]=2)[CH2:55][CH2:54]1>CN(C=O)C>[CH:53]1([CH2:56][N:57]([CH2:58][C:59]2[NH:60][C:61](=[O:69])[C:62]3[CH2:68][O:67][CH2:66][CH2:65][C:63]=3[N:64]=2)[C:15](=[O:17])[CH2:14][N:11]2[CH2:10][CH2:9][CH:8]([C:6](=[O:7])[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH2:55][CH2:54]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712264022-(4-(4-Fluorobenzoyl)piperidin-1-YL)acetic acidHCID 1362440742-[(Cyclopropylmethyl-amino)-methyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one

Product 1

HCID 136237361N-Cyclopropylmethyl-2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-N-(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-ylmethyl)-acetamideYield 21.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-acetic acid (169 mg, 0.64 mmol) was added with HATU (364 mg, 0.96 mmol) in DMF (2 mL) and DIEA (0.28 mL, 1.60 mmol) was added. This was sonicated, stirred for 30 min and then 2-[(cyclopropylmethyl-amino)-methyl]-3,5,7,8-tetrahydro-pyrano[4,3-d]pyrimidin-4-one (150 mg, 0.64 mmol) in 1 mL DMF was added to the mixture. The mixture was stirred at room temperature for 16 h, concentrated to dryness, purified by silica gel column (eluted with 0-10% methanol in dichloromethane) then triturated with methanol to give a white solid as the title compound (66 mg, 0.14 mmol, 21% yield). m/z=483.3 (M+H).

Workup

  1. additionwas added
  2. customThis was sonicated
  3. stirringThe mixture was stirred at room temperature for 16 h
  4. concentrationconcentrated to dryness
  5. custompurified by silica gel column (eluted with 0-10% methanol in dichloromethane)
  6. customthen triturated with methanol

Sources & evidence

ORD record
ord-87e0a1fbae0e40cc8a4394c981bcc53d
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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