Trifluoroacetic acid → HCID 22346919, compound

HRID 2056226Notes

Reaction equation

HRID 2056226 reaction equation
C(Cl)(=O)C(Cl)=O.[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]1[C:16]([OH:18])=[O:17].[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[N:26]([CH:38]3[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]3)[N:27]=[C:28]([C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[C:31]([O:36][CH3:37])[CH:30]=3)[C:21]=12.FC(F)(F)C(O)=O>ClCCl.O1CCCC1.CN(C)C=O.N1C=CC=CC=1>[C:16]([O-:18])(=[O:17])[CH3:8].[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[N:26]([CH:38]3[CH2:43][CH2:42][NH2+:41][CH2:40][CH2:39]3)[N:27]=[C:28]([C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:16]([C:8]4[NH:7][C:15]5[C:10]([CH:9]=4)=[CH:11][CH:12]=[CH:13][CH:14]=5)=[O:18])=[C:31]([O:36][CH3:37])[CH:30]=3)[C:21]=12

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 72899Indole-2-carboxylic acidHCID 22347369HCID 22347369, compound

Product 1

HCID 22346919HCID 22346919, compoundYield 51.9%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (0.06 mL, 0.60 mmol) was added into a solution of indole-2-carboxylic acid (0.88 g, 0.546 mmol) in dichloromethane (5 mL) and tetrahydrofuran (5 mL) at 0° C. N,N-dimethylforamide (3 drops from 0.11 mL syringe) was added and the mixture was stirred at 0° C. for 10 minutes and at ambient temperature for 20 minutes. The solvents and excess of reagents were evaporated under reduced pressure. The residue was taken into dichloromethane (2 mL) and the resulting solution (1.25 mL) was added into a solution of tert-butyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (0.12 g, 0.27 mmol) and pyridine (0.4 mL) in dichloromethane (1 mL). The mixture was stirred at ambient temperature for 2 hours. Trifluoroacetic acid (1 mL) was added and the mixture was stirred at ambient temperature for 2 hours. The solvents were evaporated under reduced pressure and the residue was purified by preparative HPLC to yield 4-(4-amino-3-{4-[(1H-2-indolylcarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)hexahydropyridinium acetate (0.07 g, 0.14 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 11.85 (br, 1H), 9.45 (s, 1H), 8.24 (d, 1H), 8.12 (d, 1H), 7.68(d, 1H), 7.48 (d, 1H), 7.40 (s, 1H), 7.35 (s, 1H), 7.30 (d, 1H), 7.24 (t, 1H), 7.09 (t, 1H), 4.77 (m, 1H), 3.97 (s, 3H), 3.11 (m, 2H), 2.68 (m, 2H), 2.09 (m, 2H), 1.89 (s, 3H), 1.84 (m, 2H); MS: MH+ 483.

Workup

  1. customThe solvents and excess of reagents were evaporated under reduced pressure
  2. stirringThe mixture was stirred at ambient temperature for 2 hours
  3. stirringthe mixture was stirred at ambient temperature for 2 hours
  4. customThe solvents were evaporated under reduced pressure
  5. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-21b125064ccf45a981643acb003301a0
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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