Trifluoroacetic acid → 5-Chloro-N2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-N4-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine

HRID 1687031Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=2)[C:5]([Cl:21])=[CH:4][N:3]=1.[CH2:22]([N:24]1[CH2:30][CH2:29][C:28]2[CH:31]=[C:32]([NH2:35])[CH:33]=[CH:34][C:27]=2[CH2:26][CH2:25]1)[CH3:23].Cl.O1CCOCC1.C(O)(C(F)(F)F)=O>COCCO>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=2)=[N:7][C:2]([NH:35][C:32]2[CH:33]=[CH:34][C:27]3[CH2:26][CH2:25][N:24]([CH2:22][CH3:23])[CH2:30][CH2:29][C:28]=3[CH:31]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of (2,5-Dichloro-pyrimidin-4-yl)-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-amine (47 mg, 0.15 mmol) in 2-methoxyethanol (3 mL) was treated with 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (28 mg, 0.15 mmol) and 4N HCl/Dioxane (0.074 mL, 0.29 mmol). The reaction mixture was heated to 120° C. and was allowed to stir for approximately 4 hours. The reaction mixture was then reduced en vacuo and the product was purified and isolated by prep HPLC to afford 44.5 mg of 5-Chloro-N*2*-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine as the TFA salt. The product was isolated as a foam, LC/MS (ESI)=474.42 (M+H). 1H NMR (400 MHz, CDCl3) δ 7.89 (t, 1H, J=7.58 Hz), 7.74 (m, 2H), 7.66 (d, 1H), 7.45 (d, 1H, J=7.83 Hz), 7.39 (s, 1H), 7.08 (s, 1H), 6.97 (m, 2H), 6.81 (d, 1H, J=8.08 Hz), 3.72 (m, 2H), 3.49 (m, 2H), 3.33 (m, 2H), 3.21 (s, 3H), 2.87 (m, 2H), 2.67 (m, 2H), 1.40 (t, 3H, J=7.07 Hz).

Workup

customthe product was purified
customisolated by prep HPLC

Sources & evidence

ORD record: ord-0217365653154296a7a2690bab3bc16b
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148391B2

Reaction notes

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