Diisopropylethylamine → HCID 49857626, compound

HRID 1466666Notes

Reaction equation

HRID 1466666 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:28][CH3:29])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][CH2:26]Cl)[N:9]=2)[CH:7]=1.Cl.[NH2:31][CH:32]1[CH2:36][CH2:35][O:34][CH2:33]1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:28][CH3:29])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][CH2:26][NH:31][CH:32]3[CH2:36][CH2:35][O:34][CH2:33]3)[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22239904Oxolan-3-amine--hydrogen chloride (1/1)HCID 66851858HCID 66851858, compound

Product 1

HCID 49857626HCID 49857626, compoundYield 30.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of N-(3-(5-chloro-2-methoxyphenyl)-1-(2-chloroethyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (0.040 g, 0.090 mmol, 1 equiv), 3-aminotetrahydrofuran hydrochloride (29 mg, 0.23 mmol, 2.50 equiv), and N,N-diisopropylethylamine (73 μL, 0.42 mmol, 4.5 equiv) in N-methylpyrrolidinone (1 mL) was heated at 100° C. After 18 h, the reaction mixture was partitioned between ethyl acetate (10 mL) and half-saturated aqueous sodium chloride solution (10 mL). The aqueous was extracted with ethyl acetate (2×10 mL). The combined organic was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by preparative HPLC provided product (13.3 mg, 30% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.67 (s, 1H), 9.32 (dd, J=7.0, 1.5 Hz, 1H), 8.77 (dd, J=4.2, 1.6 Hz, 1H), 8.65 (s, 1H), 8.31 (s, 1H), 7.49 (dd, J=8.9, 2.7 Hz, 1H), 7.40 (d, J=2.7 Hz, 1H), 7.27-7.30 (m, 2H), 4.21 (t, J=6.4 Hz, 2H), 3.85 (s, 3H), 3.60-3.76 (m, 4H), 3.38 (m, 2H), 2.96 (m, 2H), 1.96 (m, 1H), 1.62 (m, 1H). LCMS (ESI): M+H=482.2.

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate (10 mL) and half-saturated aqueous sodium chloride solution (10 mL)
  2. extractionThe aqueous was extracted with ethyl acetate (2×10 mL)
  3. dry with materialThe combined organic was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-7be0fd2c0abe4f61a66da80babe66041
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

Loading…