Ethanol → HCID 66830440, compound

HRID 1687759Notes

Reaction equation

HRID 1687759 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.[CH2:17]([O:19][C:20](=[O:36])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28]1[C:33]([Cl:34])=[CH:32][N:31]=[C:30](Cl)[N:29]=1)[CH3:18].C(O)C.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>>[CH2:17]([O:19][C:20](=[O:36])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28]1[C:33]([Cl:34])=[CH:32][N:31]=[C:30]([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:29]=1)[CH3:18]

Participants

5

Reactant 4

HCID 702EthanolHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 57974171HCID 57974171, compound

Product 1

HCID 66830440HCID 66830440, compoundYield 60%

Procedure

3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (1.00 g, 4.54 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-benzoic acid ethyl ester (1.29 g, 4.13 mmol) were dissolved in ethanol (40.00 mL, 685 mmol) and 10-camphorsulfonic acid (1.15 g, 4.95 mmol) was added. The reaction was microwaved on 300 watts, 120° C. for 40 minutes and then concentrated under reduced pressure. The residue was taken up in DCM (100 mL) and washed with sat. NaHCO3 (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by amine capped silica gel chromatography using a gradient of 0-40% EtOAc/hex as the eluting solvent to obtain 2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-benzoic acid ethyl ester as a yellow solid (1.22 g, 60%). m.p.=78-80° C.; LCMS (m/e) 496 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 11.16 (s, 1H), 8.85 (d, 1H, J=8.5 Hz), 8.14 (s, 1H), 8.11 (d, 1H, J=8.0 Hz), 7.56-7.45 (m, 1H), 7.35 (s, 1H), 7.30-7.20 (m, 1H), 7.13-7.01 (m, 2H), 6.93 (s, 1H), 4.45 (q, 2H, J=7.1 Hz), 3.60-3.50 (m, 2H), 3.39 (s, 3H), 3.0-2.88 (m, 4H), 2.80-2.67 (m, 6H), 1.45 (t, 3H, J=7.1 Hz).

Workup

  1. customThe reaction was microwaved on 300 watts, 120° C. for 40 minutes
  2. concentrationconcentrated under reduced pressure
  3. washwashed with sat. NaHCO3 (100 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by amine
  8. customcapped silica gel chromatography

Sources & evidence

ORD record
ord-b3e52db9f3994eebb055177dd46be63b
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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