Benzenemethanamine, 3-chloro- → HCID 66546707, compound

HRID 1186567Notes

Reaction equation

HRID 1186567 reaction equation
CS([C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][NH2:34]>>[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][NH:34][C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1

Participants

3

Reactant 2

HCID 77802Benzenemethanamine, 3-chloro-HCID 68227155HCID 68227155, compound

Product 1

HCID 66546707HCID 66546707, compound

Conditions

Temperature
140 °C

Procedure

The mixture of [3-(2-methanesulfonyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(2-morpholin-4-yl-ethyl)-amine (from Example 50 supra) (200 mg, 0.50 mmol) and 3-chlorobenzylamine (281 mg, 1.99 mmol) was heated at 140° C. with stirring for 2 hours. The oil was purified by chromatography (silica gel, 10 g, 200-300 mesh, eluting with dichloromethane:methanol, 50:1˜20:1) to afford the crude product (125 mg). Then the crude product was purified by prep-HPLC. Several drops of concentrated HCl were added to the fractions with product. After sonicating for several minutes, solution was concentrated under reduced pressure to afford {3-[2-(3-chloro-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-(2-morpholin-4-yl-ethyl)-amine; hydrochloride. (Yield 60 mg, 26.0%). 1H NMR (300 MHz, CD3OD): δ 8.71 (s, 1H), 8.42 (s, 1H), 8.38 (s, 1H), 7.59 (d, 1H, J=6.6 Hz), 7.49-7.28 (m, 5H), 4.87 (brs, 2H), 4.16 (brs, 2H), 3.93 (brs, 4H), 3.58-3.28 (m, 5H). LC-MS: [M+H]+ 466.

Workup

  1. customThe oil was purified by chromatography (silica gel, 10 g, 200-300 mesh, eluting with dichloromethane:methanol, 50:1˜20:1)
  2. customto afford the crude product (125 mg)
  3. customThen the crude product was purified by prep-HPLC
  4. additionSeveral drops of concentrated HCl were added to the fractions with product
  5. customAfter sonicating for several minutes
  6. concentrationsolution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d9f5d0a88be24ffc877d2cd1b7caac46
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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