Methylamine → HCID 67064763, compound

HRID 1409209Notes

Reaction equation

HRID 1409209 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][CH:21]([C:24]([OH:26])=O)[CH2:20][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].CN.C[CH2:35][N:36]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[OH:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:19][CH2:20][CH:21]([C:24]([NH:36][CH3:35])=[O:26])[CH2:22][CH2:23]3)[N:15]3[N:27]=[CH:28][CH:29]=[C:14]3[N:13]=2)=[O:10])=[CH:30][CH:31]=1)([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 44250957HCID 44250957, compound2×

Product 1

HCID 67064763HCID 67064763, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(5-(4-(2-hydroxypropan-2-yl)benzamido)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-4-carboxylic acid (Compound 244, 80 mg, 0.189 mmol), methylamine (33 μL, 0.378 mmol), EDCI (72 mg, 0.378 mmol), and HOBT (13 mg, 0.094 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, 30-50% (MeCN/H2O gradient+0.01% TFA) provided the titled compound as a yellow oil (45 mg, 55%). 1H NMR (DMSO-d6) δ: 10.90 (s, 1H), 8.09 (d, J=2.3 Hz, 1H), 8.00 (d, J=8.8 Hz, 2H), 7.80-7.87 (m, 1H), 7.60 (d, 2H), 7.41 (s, 1H), 6.35 (d, J=2.3 Hz, 1H), 4.46 (d, J=12.1 Hz, 2H), 3.10 (td, J=12.3, 2.8 Hz, 2H), 2.59 (d, J=4.5 Hz, 3H), 1.71-1.90 (m, 4H), 1.44 (s, 6H). ESI-MS: m/z 437.0 (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, 30-50% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-7b3487a617cc4094bfcfb69afb47bd8f
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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