Hydrochloric Acid → N-((1R,2R)-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-2,2,2-trifluoro-acetamide

HRID 1040909Notes

Reaction equation

HRID 1040909 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[C:5]([Cl:22])=[CH:4][N:3]=1.[CH3:23][O:24][CH2:25][CH2:26][N:27]1[CH2:33][CH2:32][C:31]2[CH:34]=[C:35]([NH2:38])[CH:36]=[CH:37][C:30]=2[CH2:29][CH2:28]1.Cl.CCOCC>COCCO.O1CCOCC1>[Cl:22][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])=[N:7][C:2]([NH:38][C:35]2[CH:36]=[CH:37][C:30]3[CH2:29][CH2:28][N:27]([CH2:26][CH2:25][O:24][CH3:23])[CH2:33][CH2:32][C:31]=3[CH:34]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 86633893HCID 86633893, compound

Product 1

HCID 56663172N-((1R,2R)-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-2,2,2-trifluoro-acetamide

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-2,2,2-trifluoro-acetamide (776 mg, 2.17 mmol) was added into a Vial, followed by a solution of 3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (447 mg, 2.03 mmol) in 2-Methoxyethanol (15 mL). 4.00 M of Hydrogen chloride in 1,4-Dioxane (1.1 mL) was added and the reaction was heated at 120° C. After 3 h, the reaction was cooled to room temperature, and 85 mL ether was added. The HCl salt formed as an oil, not a solid, so it was redissolved by adding MeOH and DCM. Macroporous carbonate resin (3.16 mmol/g loading; 2.45 g, 7.7 mmol) was then added and stirred for 1 h and filtered before concentration. The residue was dissolved in DCM, then chromatographed (2×12 g SiO2, ISCO, 0-10% MeOH:DCM) to afford N-((1R,2R)-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-2,2,2-trifluoro-acetamide (414 mg, 38%) as a beige solid. m.p.=180-182° C.; LCMS (m/e) 541 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.92 (s, 1H), 7.88 (m, 1H), 7.23 (s, 1H), 7.22 (d, 1H, J=8.5 Hz), 7.04 (d, 1H, J=8.5 Hz), 6.81 (s, 1H), 5.22 (d, 1H, J=7.5 Hz), 4.0 (m, 1H), 3.68 (m, 1H), 3.54 (t, 1H, J=5.5 Hz), 3.36 (s, 3H), 2.92 (m, 4H), 2.74 (m, 4H), 2.28 (m, 1H), 2.15 (m, 1H), 1.80 (m, 4H), 1.2-1.5 (m, 4H).

Workup

  1. temperaturethe reaction was cooled to room temperature

Sources & evidence

ORD record
ord-2b0de50a146e45138b72c14e2705ca80
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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