Dimethylamine → HCID 67064682, compound

HRID 1256372Notes

Reaction equation

HRID 1256372 reaction equation
[OH:1][C:2]([C:5]1[CH:31]=[CH:30][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([OH:26])=O)[CH2:19]3)[N:15]3[N:27]=[CH:28][CH:29]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].[CH3:32][NH:33][CH3:34].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[OH:1][C:2]([C:5]1[CH:31]=[CH:30][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([N:33]([CH3:34])[CH3:32])=[O:26])[CH2:19]3)[N:15]3[N:27]=[CH:28][CH:29]=[C:14]3[N:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67064096HCID 67064096, compound2×

Product 1

HCID 67064682HCID 67064682, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (R)-1-(5-(4-(2-hydroxypropan-2-yl)benzamido)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-3-carboxylic acid (Compound 84, 100 mg, 0.236 mmol), dimethylamine (236 μL, 0.472 mmol), EDCI (90 mg, 0.472 mmol), and HOBT (16 mg, 0.118 mmol) in DMF (4 mL) were stirred for 12 hours at room temperature. The reaction was complete as determined by LCMS analysis. The reaction mixture was then partitioned between ethyl acetate and water and the separated organic layer was dried over Mg2SO4, filtered, and concentrated under reduced pressure. Purification by preparatory HPLC, 20-40% (MeCN/H2O gradient+0.01% TFA) provided the titled compound as a white solid (71 mg, 69%). 1H NMR (DMSO-d6) δ: 10.91 (s, 1H), 8.08 (d, J=2.3 Hz, 1H), 7.95-8.03 (m, J=8.6 Hz, 2H), 7.60 (d, J=8.8 Hz, 2H), 7.37 (s, 1H), 6.36 (d, J=2.0 Hz, 1H), 4.55 (br. s., 1H), 4.35 (br. s., 1H), 2.97-3.18 (m, 6H), 2.83 (s, 3H), 1.57-2.01 (m, 4H), 1.45 (s, 6H). ESI-MS: m/z 451.0 (M+H)+.

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and water
  2. dry with materialthe separated organic layer was dried over Mg2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by preparatory HPLC, 20-40% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-e8fb808247ed4e4faf12bdfa57f8f970
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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