Triethylamine → Tert-butyl (6-fluoro-4-(2-(5-fluoro-2-(2-(2-oxo-2,3-dihydro-1H-imidazol-1-yl)ethylamino)pyrimidin-4-yl)benzo[b]thiophen-7-yl)pyridin-3-yl)methyl(methyl)carbamate

HRID 561031Notes

Reaction equation

[C:1]([O:5][C:6](=[O:34])[N:7]([CH2:9][C:10]1[CH:11]=[N:12][C:13]([F:33])=[CH:14][C:15]=1[C:16]1[C:21]2[S:22][C:23]([C:25]3[C:30]([F:31])=[CH:29][N:28]=[C:27](Cl)[N:26]=3)=[CH:24][C:20]=2[CH:19]=[CH:18][CH:17]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.FC(F)(F)C(O)=O.[NH2:49][CH2:50][CH2:51][N:52]1[CH:56]=[CH:55][NH:54][C:53]1=[O:57]>C(O)CCC>[F:33][C:13]1[N:12]=[CH:11][C:10]([CH2:9][N:7]([CH3:8])[C:6](=[O:34])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[C:15]([C:16]2[C:21]3[S:22][C:23]([C:25]4[C:30]([F:31])=[CH:29][N:28]=[C:27]([NH:49][CH2:50][CH2:51][N:52]5[CH:56]=[CH:55][NH:54][C:53]5=[O:57])[N:26]=4)=[CH:24][C:20]=3[CH:19]=[CH:18][CH:17]=2)[CH:14]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Combine {4-[2-(2-chloro-5-fluoro-pyrimidin-4-yl)-benzo[b]thiophen-7-yl]-6-fluoro-pyridin-3-ylmethyl}-methyl-carbamic acid tert-butyl ester (0.52 g, 1.04 mmol) and triethylamine (0.87 mL, 6.24 mmol) in n-butanol (10.0 mL). Add 1-(2-amino-ethyl)-1,3-dihydro-imidazol-2-one; compound with trifluoro-acetic acid (0.75 g, 3.12 mmol). Heat the reaction mixture at 120° C. for 54 hours for completion, then cool to room temperature. Remove solvent on a rotovap to obtain the crude product. Purify the crude by column chromatography (0.5% to 6% 2 M NH3 in methanol solution in dichloromethane) to afford the desired product (0.28 g). MS (ES) m/z 594 [M+1]+.

Workup

temperaturecool to room temperature
customRemove solvent on a rotovap to obtain the crude product
customPurify the crude by column chromatography (0.5% to 6% 2 M NH3 in methanol solution in dichloromethane)

Sources & evidence

ORD record: ord-93b82d6d103f4306b3bfb940770e1ea4
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063212B2

Reaction notes

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