Methylamine → N1-methyl-2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}acetamide

HRID 51600Notes

Reaction equation

[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:24]3[CH2:29][CH2:28][CH:27]([CH2:30][C:31]([OH:33])=O)[CH2:26][CH2:25]3)[C:4]=2[N:5]=[CH:6][N:7]=1.O[N:35]1[C:39]2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN.O1CCCC1>CN(C)C=O>[CH3:39][NH:35][C:31](=[O:33])[CH2:30][CH:27]1[CH2:28][CH2:29][CH:24]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9]2)[CH2:25][CH2:26]1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}acetic acid (0.094 g, 0.21 mmol), 1-hydroxy-7-azabenzotriazole (0.044 g, 0.32 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.082 g, 0.43 mmol), 2M methylamine in tetrahydrofuran (2.13 mL, 4.26 mmol) and N,N-dimethylformamide (1.50 mL) was heated at 60° C. overnight. The mixture was allowed to cool to ambient temperature and purified by preparative RP-HPLC to yield N1-methyl-2-{4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexyl}acetamide (0.025 g, 0.055 mmol) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.24(s, 1H), 7.42(d, 2H), 7.38 (t, 2H), 7.16(t, 1H), 7.07(m, 5H), 5.82(br, 2H), 5.62(br, 1H), 4.70(m, 1H), 2.83 (d, 3H), 2.36-1.70(m, 11H); MS: MH+ 456; TLC (ethyl acetate) Rf 0.34; RP-HPLC (Hypersil C18, 5 μm, 100 A, 250×4.6 mm; 25%-100% acetonitrile-0.05M ammonium acetate over 10 min, 1 mL/min) Rt 9.32 min.

Workup

temperatureto cool to ambient temperature
custompurified by preparative RP-HPLC

Sources & evidence

ORD record: ord-378dcdb8b098476b9806323d8da06beb
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06713474B2

Reaction notes

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