Triethylamine → (R)-1-[4-(7-Dimethylsulfamoyl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetate

HRID 394532Notes

Reaction equation

HRID 394532 reaction equation
[CH3:1][N:2]([CH3:16])[S:3]([C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][NH:12][CH2:13]2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].[C:17]([O:20][C@@H:21]([C:23]1[N:28]=[C:27](Cl)[CH:26]=[CH:25][N:24]=1)[CH3:22])(=[O:19])[CH3:18].C(N(CC)CC)C>C(O)(C)C>[C:17]([O:20][C@@H:21]([C:23]1[N:24]=[C:25]([N:12]2[CH2:11][CH2:10][C:9]3[C:14](=[CH:15][C:6]([S:3](=[O:5])(=[O:4])[N:2]([CH3:16])[CH3:1])=[CH:7][CH:8]=3)[CH2:13]2)[CH:26]=[CH:27][N:28]=1)[CH3:22])(=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 21393856N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamideHCID 54154993(R)-1-(4-chloropyrimidin-2-yl)-ethyl acetate

Product 1

HCID 69735145(R)-1-[4-(7-Dimethylsulfamoyl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetateYield 92%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid dimethylamide (prepared according to the method of Example 247, Step B, 210 mg, 0.88 mmol) in isopropanol (5 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl acetate (prepared according to the method of Preparation Five, 175 mg, 0.88 mmol) followed by triethylamine (0.24 mL, 1.75 mmol). This mixture was stirred at room temperature for 1.75 h then heated to reflux for 1.5 h, cooled to room temperature, evaporated, and purified by flash column chromatography (1% methanol/chloroform) to give 327 mg (92%) of the title compound of Example 247, Step C as a white solid. 1H NMR (CDCl3, 250 MHz) δ 8.28 (d, 1H), 7.68-7.58 (c, 2H), 7.47 (d, 1H), 6.44 (d, 1H), 5.72 (q, 1H), 4.86 (s, 2H), 3.92 (t, 2H), 3.05 (t, 2H), 2.73 (s, 6H), 2.19 (s, 3H), 1.62 (d, 3H); MS (TS) 431 (MH+).

Workup

  1. customprepared
  2. customaccording to the method of Preparation Five, 175 mg, 0.88 mmol)
  3. temperaturethen heated
  4. temperatureto reflux for 1.5 h
  5. temperaturecooled to room temperature
  6. customevaporated
  7. custompurified by flash column chromatography (1% methanol/chloroform)

Sources & evidence

ORD record
ord-13272f04e8f64fee998454bae074b4ed
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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