Ethylamine → HCID 66878213, compound

HRID 1409219Notes

Reaction equation

HRID 1409219 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].[CH2:32]([NH2:34])[CH3:33].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH2:32]([NH:34][C:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16]2[N:15]3[N:27]=[CH:28][CH:29]=[C:14]3[N:13]=[C:12]([NH:11][C:9](=[O:10])[C:8]3[CH:30]=[CH:31][C:5]([C:2]([OH:1])([CH3:3])[CH3:4])=[CH:6][CH:7]=3)[CH:17]=2)[CH2:19]1)=[O:26])[CH3:33]

Participants

6

Reactant 4

HCID 6341EthylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 67064096HCID 67064096, compound2×

Product 1

HCID 66878213HCID 66878213, compoundYield 8.3%

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), ethylamine (11 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 (8.8 mg, 8%). Melting point (227.8-228.7° C.). 1H NMR (DMSO-d6) δ: 10.89 (s, 1H), 8.10 (d, J=2.3 Hz, 1H), 8.05 (t, J=5.4 Hz, 1H), 8.00 (d, J=8.6 Hz, 2H), 7.56-7.65 (m, 2H), 7.41 (s, 1H), 6.36 (d, J=2.3 Hz, 1H), 4.31 (br. s., 2H), 3.29 (dd, J=12.0, 10.5 Hz, 2H), 2.93-3.17 (m, 4H), 1.92 (br. s., 1H), 1.77-1.87 (m, 1H), 1.73 (br. s., 2H), 1.45 (s, 6H), 1.02 (t, J=7.3 Hz, 3H). 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, 25-35% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-53ef0941c4d24d0da031ca96f28d359c
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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