Isopropylamine → HCID 67064321, compound

HRID 1256369Notes

Reaction equation

HRID 1256369 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](O)=[O:25])[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].[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[CH2:19][CH2:20][CH:21]([C:24]([NH:35][CH:32]([CH3:34])[CH3:33])=[O:25])[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)([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 44250957HCID 44250957, compound2×

Product 1

HCID 67064321HCID 67064321, compoundYield 8.3%

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), isopropylamine (22 mg, 0.378 mmol), EDCI (72 mg, 0.378 mmol), and HOBT (13 mg, 0.095 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, 20-30% (MeCN/H2O gradient+0.01% TFA) provided the titled compound as a white solid (7.3 mg, 8%). 1H NMR (DMSO-d6) δ: 10.88 (s, 1H), 8.08 (d, J=2.3 Hz, 1H), 7.99 (d, J=8.8 Hz, 2H), 7.74 (d, J=7.8 Hz, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.42 (s, 1H), 6.34 (d, J=2.3 Hz, 1H), 4.43-4.50 (m, 3H), 3.84 (dd, J=14.3, 6.4 Hz, 2H), 3.07 (br. s., 2H), 1.73-1.87 (m, 4H), 1.45 (s, 6H), 1.05 (d, J=6.6 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, 20-30% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-b675a28db8544b909f681c14e55f44ed
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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