Trifluoroacetic acid → 5-[(4-Aminopiperidin-1-yl)methyl]-n-[(1r)-1-phenylethyl]pyrrolo-[2,1-f][1,2,4]triazin-4-amine

HRID 859232Notes

Reaction equation

[Br-].Cl[C:3]1[C:8]2=[C:9]([CH2:12][N+:13]([CH2:18][CH3:19])([CH2:16][CH3:17])CC)[CH:10]=[CH:11][N:7]2[N:6]=[CH:5][N:4]=1.[C:20]1([C@H:26]([NH2:28])[CH3:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C[CH2:30][N:31](C(C)C)C(C)C.N1CCC(NC(=O)OC(C)(C)C)CC1.C(O)(C(F)(F)F)=O>CC(N(C)C)=O>[NH2:31][CH:30]1[CH2:17][CH2:16][N:13]([CH2:12][C:9]2[CH:10]=[CH:11][N:7]3[C:8]=2[C:3]([NH:28][C@@H:26]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:27])=[N:4][CH:5]=[N:6]3)[CH2:18][CH2:19]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of Compound 1A (100 mg, 0.29 mmol) and (R)-1-phenylethanamine (34.9 mg, 0.29 mmol) in 0.6 mL of DMA was added DIEA (37.2 mg, 0.29 mmol). The mixture was stirred at room temperature for 17 h upon which time DIEA (74.4 mg, 0.58 mmol) and tert-butyl piperidine-4-ylcarbamate (86.4 mg, 0.43 mmol) were added. The mixture was heated at 70° C. for 3 h and cooled to room temperature. TFA (2.00 mL, 260 mmol) was added and the mixture was stirred at room temperature for 1 h. The mixture was concentrated in vacuo and the residue was purified by prep HPLC to give Compound 1C in 62% yield. Compound 1C had an analytical HPLC retention time=1.58 min. (YMC S5 ODS column 4.6×50 mm, 10–90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 ml/min, monitoring at 220 nm) and a LC/MS M++1=351.

Workup

additionwere added
temperaturecooled to room temperature
concentrationThe mixture was concentrated in vacuo
customthe residue was purified by prep HPLC

Sources & evidence

ORD record: ord-f9c5f1327b614afc877f7fc0b2ad0051
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07151176B2

Reaction notes

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