Diisopropylethylamine → {3-[5-Chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl ester

HRID 1986200Notes

Reaction equation

HRID 1986200 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[C:15]3[CH:14]=[C:13]([C:16]4[C:21]([Cl:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[C:24]([O:28][C:29](=[O:35])[NH:30][CH2:31][CH2:32][CH2:33][NH2:34])([CH3:27])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C>O1CCOCC1.ClCCl>[C:24]([O:28][C:29](=[O:35])[NH:30][CH2:31][CH2:32][CH2:33][NH:34][C:18]1[N:17]=[C:16]([C:13]2[S:12][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([C:5](=[O:6])[NH:4][CH:1]4[CH2:3][CH2:2]4)[C:15]=3[CH:14]=2)[C:21]([Cl:22])=[CH:20][N:19]=1)([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 866253512-(2,5-Dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

Product 1

HCID 68905864{3-[5-Chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl esterYield 65.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
97 °C

Procedure

A stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (5.59 g, 15.3 mmol) in 1.4-dioxane (60 mL), (3-amino-propyl)-carbamic acid tert-butyl ester (2.70 mL, 2.69 mg, 15.5 mmol) in N,N-diisopropylethylamine (5.20 mL, 3.86 g, 29.9 mmol) is heated at 97° C. for 120 hours. The mixture is then cooled to room temperature, diluted with dichloromethane (120 mL), filtered, washed with dichloromethane (2×25 mL), and dried to provide {3-[5-chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl ester (5.00 g, 65%). This intermediate (4.99 g, 9.94 mmol) is suspended in methanol (120 mL) and treated with 10% aqueous HCl (10 mL) and the mixture is heated at 100° C. for 24 hours. The mixture is then cooled to room temperature, quenched with 2 N NaOH (20 mL), filtered, washed with H2O (60 mL), dichloromethane (60 mL), and diethyl ether (60 mL), and dried to provide the title compound (3.99 g, 99%).

Workup

  1. temperatureThe mixture is then cooled to room temperature
  2. filtrationfiltered
  3. washwashed with dichloromethane (2×25 mL)
  4. customdried

Sources & evidence

ORD record
ord-96cebf09134a4a918fc73586063a40fa
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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