Hydrochloric Acid → HCID 56673544, compound

HRID 1040814Notes

Reaction equation

HRID 1040814 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1.Cl[C:18]1[N:23]=[C:22]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]2[OH:31])[C:21]([Cl:32])=[CH:20][N:19]=1.Cl.O1CCOCC1>CC(O)C>[Cl:32][C:21]1[C:22]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]2[OH:31])=[N:23][C:18]([NH:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:11][CH2:10][C:9]=3[CH:12]=2)=[N:19][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 86633877HCID 86633877, compound

Product 1

HCID 56673544HCID 56673544, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (76 mg, 0.34 mmol) and trans-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexanol (100 mg, 0.38 mmol, 1.1 eq) were dissolved in IPA (3 mL). 4.0 M HCl in dioxane (95 μL, 0.38 mmol, 1.1 eq) was added and the reaction was heated at 140° C. in a microwave for 2.5 hours. The reaction was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (20 mL) and washed with sat. NaHCO3 (20 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-100% EtOAc/hex as the eluting solvent to obtain trans-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexanol as a pink foam (42 mg, 28%). LCMS (m/e) 446 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.93 (s, 1H), 7.35-7.22 (m, 2H), 7.04 (d, 1H, J=8.1 Hz), 6.78 (s, 1H), 5.17 (d, 1H, J=7.1 Hz), 3.96-3.85 (m, 1H), 3.60-3.54 (m, 2H), 3.38 (s, 3H), 3.00-2.85 (m, 4H), 2.81-2.65 (m, 6H), 2.20-2.10 (m, 2H), 1.85-1.77 (m, 2H), 1.45-1.10 (m, 5H).

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. washwashed with sat. NaHCO3 (20 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by basic alumina chromatography

Sources & evidence

ORD record
ord-ee6a6bb006b344bab1a0e18d05bddf85
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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