Trifluoroacetic acid → HCID 67479148, compound

HRID 472452Notes

Reaction equation

HRID 472452 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][NH:14][C:15]1[C:16]2[N:17]([N:21]=[C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)=[CH:27][CH:26]=3)[N:23]=2)[CH:18]=[CH:19][CH:20]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:37][N:34]1[CH2:35][CH2:36][N:31]([C:28]2[CH:27]=[CH:26][C:25]([NH:24][C:22]3[N:23]=[C:16]4[C:15]([NH:14][CH2:13][CH:9]5[CH2:10][CH2:11][CH2:12][NH:8]5)=[CH:20][CH:19]=[CH:18][N:17]4[N:21]=3)=[CH:30][CH:29]=2)[CH2:32][CH2:33]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67478843HCID 67478843, compound

Product 1

HCID 67479148HCID 67479148, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

170 c) To a solution of 2-({2-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (90.0 mg, 0.178 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.0547 mL, 0.710 mmol). The mixture was stirred at room temperature for 18 hours then the volatiles were evaporated under reduced pressure. Crude N(2)-[4-(4-Methyl-piperazin-1-yl)-phenyl]-N(8)-pyrrolidin-2-ylmethyl-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine as the bis-trifluoroacetic acid salt was isolated as a red-brown resin. The residue was suspended in dichloromethane (2 mL) and triethylamine (0.148 mL, 1.06 mmol) was added. The mixture was cooled to 5° C. and methanesulfonyl chloride (0.0165 mL, 0.213 mmol) was added. The mixture was stirred for 1 hour at 5° C. then warmed to room temperature and stirred for 1 hour. The reaction mixture was poured into saturated aqueous sodium carbonate (10 mL) and extracted with dichloromethane (3×10 mL). The combined organic layers were washed with water (10 mL) then saturated aqueous sodium chloride (10 mL), dried over magnesium sulfate, filtered and evaporated to a dark resin. The residue was purified via reverse phase chromatography using a Gilson apparatus (0%→50% acetonitrile:water (w/0.1% TFA modifier)). Collected desired fractions, basified with saturated aqueous sodium carbonate and extracted with dichloromethane (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated. N(8)-(1-Methanesulfonyl-pyrrolidin-2-ylmethyl)-N(2)-[4-(4-methyl-piperazin-1-yl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was isolated as a pale yellow foam (0.033 g, 38%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.80 (d, J=6.5 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 6.96 (d, J=8.9 Hz, 2H), 6.71 (t, J=7.4 Hz, 1H), 6.55 (d, J=7.9 Hz, 1H), 6.52 (s, 1H), 5.09 (t, J=6.4 Hz, 1H), 4.03-3.94 (m, 1H), 3.63-3.55 (m, 1H), 3.53-3.46 (m, 1H), 3.39-3.25 (m, 2H), 3.18-3.13 (m, 4H), 2.88 (s, 3H), 2.62-2.57 (m, 4H), 2.36 (s, 3H), 2.11-1.91 (m, 4H). MS=485 (MH)+.

Workup

  1. customthe volatiles were evaporated under reduced pressure

Sources & evidence

ORD record
ord-155dacebe39941b3927d8a13acda6be3
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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