Triethylamine → (R)-1-[4-(6-Thiophen-3-yl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetate

HRID 394535Notes

Reaction equation

HRID 394535 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[CH2:13][NH:12][CH2:11][CH2:10]3)=[CH:3]1.[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][CH:16]=[C:7]([C:4]4[CH:5]=[CH:6][S:2][CH:3]=4)[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 223286436-thiophen-3-yl-3,4-dihydro-1H-isoquinoline hydrochlorideHCID 54154993(R)-1-(4-chloropyrimidin-2-yl)-ethyl acetate

Product 1

HCID 20767625(R)-1-[4-(6-Thiophen-3-yl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetateYield 98%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 6-thiophen-3-yl-3,4-dihydro-1H-isoquinoline hydrochloride (prepared according to the method of Example 248, Step B, 170 mg, 0.68 mmol) in isopropanol (6 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl acetate (prepared according to the method of Preparation Five, 136 mg, 0.68 mmol) followed by triethylamine (0.28 mL, 2.04 mmol). This mixture was stirred at reflux for 7 h, cooled to room temperature overnight, evaporated, and purified by flash column chromatography (0.5→1% methanol/chloroform) to give 253 mg (98%) of the title compound of Example 248, Step C as a yellow solid. 1H NMR (CDCl3, 250 MHz) δ 8.26 (d, 1H), 7.52-7.36 (c, 6H), 6.43 (d, 1H), 5.73 (q, 1H), 4.76 (s, 2H), 3.96-3.82 (c, 2H), 3.02 (t, 2H), 2.21 (s, 3H), 1.63 (d, 3H); MS (TS) 380 (MH+).

Workup

  1. customprepared
  2. customaccording to the method of Preparation Five, 136 mg, 0.68 mmol)
  3. temperatureat reflux for 7 h
  4. customevaporated
  5. custompurified by flash column chromatography (0.5→1% methanol/chloroform)

Sources & evidence

ORD record
ord-0f8dad6e0c9145c1837b088f8344c25a
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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