Diisopropylethylamine → HCID 21068457, compound

HRID 1373443Notes

Reaction equation

HRID 1373443 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[C:10](Cl)=[CH:9][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[Cl:18])=[N:7][C:6]=12.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[CH2:32][CH2:33][NH2:34])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(C(C)C)CC)(C)C>O1CCOCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[CH2:32][CH2:33][NH:34][C:10]1[N:5]2[N:4]=[CH:3][C:2]([Br:1])=[C:6]2[N:7]=[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[CH:9]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 27564212-(AMINOETHYL)-1-N-BOC-PIPERIDINEHCID 21930988HCID 21930988, compound

Product 1

HCID 21068457HCID 21068457, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

3-Bromo-7-chloro-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidine (400 mg, 1.166 mmoles) (prepared as described in Preparative Example 129) was dissolved in anhydrous 1,4-dioxane (5.7 mL). 2-Aminoethylpiperidine-1-carboxylic acid tert-butyl ester (266 mg, 1.166 mmoles) and diisopropyl ethylamine (0.409 mL, 2.33 mmoles) were added and the mixture was heated at 75° C. for 48h. Additional diisopropyl ethylamine (0.204 mL, 1.166 mmoles) was added and the heating was continued for a total of 58h. The solution was evaporated to dryness and the residue was chromatographed on a silica gel column (15×5 cm) using dichloromethane followed by 0.3% (10% conc. ammonium hydroxide in methanol)-dichloromethane as the eluant to give 2-{[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino]ethyl}piperidine-1-carboxylic acid tert-butyl ester (491.1 mg, 79%): FABMS: m/z 534.1 (MH+); HRESIMS: m/z 534.12797 (MH+). Calcd. for C24H30N5O2BrCl: m/z 534.12714; δH (CDCl3) 1.50 (1H, m, CH2), 1.51 (9H, s, COOC(CH3)3), 1.57 (2H, m, CH2), 1.68 (2H, m, CH2), 1.76 (2H, m, CH2), 2.24 (1H, bm, CH2), 2.82/3.40/3.54/4.08/4.51 (5H, m, CH/CH2), 6.34 (1H, s, H6), 7.41 (2H, m, Ar—H), 7.51 (1H, m, Ar—H), 7.76 (1H, m, Ar—H) and 8.08 ppm (1H, s, H2); δC (CDCl3) CH3: 28.5, 28.5, 28.5; CH2: 19.2, 25.5, 29.2, 29.2, 39.2, 67.1; CH: ˜47.4, 87.1, 127.1, 130.1, 130.1, 131.6, 143.9; C, 80.0, 83.0, 132.1, 138.9, 145.7, 146.2, 158.0.

Workup

  1. customwas continued for a total of 58h
  2. customThe solution was evaporated to dryness
  3. customthe residue was chromatographed on a silica gel column (15×5 cm)

Sources & evidence

ORD record
ord-b8b8635587d54ecb9bb603967e669da8
Source dataset
uspto-grants-2007_01
Patent number
US07161003B1

Reaction notes

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