Isopropylamine → HCID 67064190, compound

HRID 1409215Notes

Reaction equation

HRID 1409215 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].[CH:32]([NH2:35])([CH3:34])[CH3:33].CCN=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[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:35][CH:32]([CH3:34])[CH3:33])=[O:26])[CH2:19]3)[N:15]3[N:27]=[CH:28][CH:29]=[C:14]3[N:13]=2)=[O:10])=[CH:30][CH:31]=1)([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67064096HCID 67064096, compound2×

Product 1

HCID 67064190HCID 67064190, compoundYield 39.2%

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), isopropylamine (14 mg, 0.236 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, 25-35% (MeCN/H2O gradient+0.01% TFA) provided the titled compound as a white solid (43 mg, 39%). 1H NMR (DMSO-d6) δ: 10.92 (s, 1H), 8.10 (d, J=2.3 Hz, 1H), 7.97-8.04 (m, 2H), 7.92 (d, J=7.6 Hz, 1H), 7.55-7.66 (m, 2H), 7.39 (s, 1H), 6.37 (d, J=2.3 Hz, 1H), 4.26 (t, J=12.4 Hz, 2H), 3.84 (dq, J=13.8, 6.7 Hz, 1H), 3.36 (dd, J=12.4, 10.4 Hz, 1H), 2.98-3.14 (m, 1H), 2.53-2.58 (m, 1H), 1.67-2.01 (m, 4H), 1.39-1.51 (m, 6H), 1.05 (t, J=6.2 Hz, 6H). ESI-MS: m/z 465.0 (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, 25-35% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-7f5b119fc5084ed891f3c943a23e3aa3
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…