Trifluoroacetic acid → 4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylbenzamide

HRID 2363300Notes

Reaction equation

HRID 2363300 reaction equation
[C:1]([CH2:3][C:4]1([N:20]2[CH:24]=[C:23]([C:25]3[C:26]4[CH:33]=[CH:32][N:31](COCC[Si](C)(C)C)[C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:7][N:6]([C:8]2[CH:19]=[CH:18][C:11]([C:12]([NH:14][CH:15]([CH3:17])[CH3:16])=[O:13])=[CH:10][CH:9]=2)[CH2:5]1)#[N:2].FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]([CH2:3][C:4]1([N:20]2[CH:24]=[C:23]([C:25]3[C:26]4[CH:33]=[CH:32][NH:31][C:27]=4[N:28]=[CH:29][N:30]=3)[CH:22]=[N:21]2)[CH2:5][N:6]([C:8]2[CH:9]=[CH:10][C:11]([C:12]([NH:14][CH:15]([CH3:17])[CH3:16])=[O:13])=[CH:18][CH:19]=2)[CH2:7]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 711435494-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylbenzamide

Product 1

HCID 711436414-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-{3-(Cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-isopropylbenzamide (1.74 g, 3.05 mmol) was dissolved in methylene chloride (5.0 mL) and trifluoroacetic acid (5.0 mL, 26 mmol) and stirred at room temperature After 4 hours, LC/MS data indicated that the reaction was complete and the desired product was formed (LCMS (M+H)+: m/z=471.3). The volatiles were removed in vacuo and the residue was azeotropically washed with acetonitrile several times (4×10 mL) to remove the excess TFA. The residue was dissolved in methanol (15 mL) and to this was added 14.8 M ammonium hydroxide in H2O (3.0 mL, 44 mmol) and ethylenediamine (0.10 mL, 1.5 mmol) and the resulting solution was stirred at room temperature for 3 hours to afford the desired product. The product was further precipitated out as a white solid by the addition of H2O (15 mL) and the heterogeneous solution was stirred for 30 minutes prior to pouring into water (60 mL). The precipitate was filtered off, washed with water (2×10 mL), and dried under high vacuum to afford the desired product (1.05 g, 78% yield). LCMS (M+H)+: m/z=441.1. 1H NMR (400 MHz, CD3OD): δ 8.78 (s, 1H), 8.66 (s, 1H), 8.42 (s, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.75 (d, J=8.5 Hz, 2H), 7.50 (d, J=4.0 Hz, 1H), 7.00 (d, =4.0 Hz, 1H), 6.64 (t, J=8.5 Hz, 2H), 4.55 (d, J=8.0 Hz, 2H), 4.40 (d, J=8.0 Hz, 2H), 4.19 (m, 1H), 3.62 (s, 2H), 1.22 (d, J=7.0 Hz, 6H).

Sources & evidence

ORD record
ord-acbadd802fe445098f08b85eefc065b1
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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