1-Hydroxybenzotriazole → HCID 68856653, compound

HRID 1986301Notes

Reaction equation

HRID 1986301 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]([NH:23][CH2:24][CH2:25][CH2:26][NH2:27])[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[C:28]([O:32][C:33]([N:35]1[CH2:39][CH2:38][C@H:37]([C:40](O)=[O:41])[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C(N(CC)C(C)C)(C)C.Cl.C(N(CC)CCCN=C=NCC)C.ON1C2C=CC=CC=2N=N1>ClCCl>[C:28]([O:32][C:33]([N:35]1[CH2:39][CH2:38][C@H:37]([C:40](=[O:41])[NH:27][CH2:26][CH2:25][CH2:24][NH:23][C:18]2[N:17]=[C:16]([C:13]3[S:12][C:11]4[CH:10]=[CH:9][CH:8]=[C:7]([C:5](=[O:6])[NH:4][CH:1]5[CH2:2][CH2:3]5)[C:15]=4[CH:14]=3)[C:21]([Cl:22])=[CH:20][N:19]=2)[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1512492(3S)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 99645121-(3-Diethylaminopropyl)-3-ethylcarbodiimide hydrochlorideHCID 68856149HCID 68856149, compound

Product 1

HCID 68856653HCID 68856653, compoundYield 90.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirred suspension of 2-[2-(3-aminopropylamino)-5-chloropyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (500 mg, 1.24 mmol) in dichloromethane (30 mL) is treated at room temperature with (S)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (333 mg, 1.55 mmol), N,N-diisopropylethylamine (0.220 mL, 1.26 mmol), 1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride (240 mg, 1.25 mmol) and 1-hydroxybenzotriazole (171 mg, 1.21 mmol) for 24 hours. The mixture is then diluted with dichloromethane (30 mL), filtered, washed with water (30 mL) and diethyl ether (30 mL), and dried to provide (S)-3-{3-[5-chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propylcarbamoyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (670 mg, 90%). A stirred mixture of this intermediate (665 mg, 1.11 mmol) in dichloromethane (25 mL) is treated at room temperature with TFA (2.5 mL) for 72 hours. The mixture is then concentrated under reduced pressure and subjected to chromatographic purification on silica gel, eluting with 2 M NH3/MeOH in dichloromethane: 16-40%, to provide the title compound (474 mg, 82% yield). ES+(m/z) 499 (35Cl) and 501 (37Cl) [M+H].

Workup

  1. filtrationfiltered
  2. washwashed with water (30 mL) and diethyl ether (30 mL)
  3. customdried

Sources & evidence

ORD record
ord-18e9d2c00c1544ed9e335f7e44cf9875
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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