Triethylamine → HCID 57881268, compound

HRID 1817711Notes

Reaction equation

HRID 1817711 reaction equation
[CH2:1]([C:8]1[N:13]=[C:12]([CH2:14][CH2:15][OH:16])[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1CCCCO1)CC#C.[N:35]([CH2:38][CH2:39][C:40]1[CH:45]=[C:44]([C:46]2[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=2)[N:43]=[C:42]([CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[N:41]=1)=[N+]=[N-].[CH3:60][S:61](Cl)(=[O:63])=[O:62].CCN(CC)CC>C1COCC1.CCOC(C)=O>[CH2:53]([C:42]1[N:41]=[C:40]([CH2:39][CH2:38][NH2:35])[CH:45]=[C:44]([C:46]2[CH:47]=[CH:48][C:49]([CH3:52])=[CH:50][CH:51]=2)[N:43]=1)[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1.[CH2:1]([C:8]1[N:13]=[C:12]([CH2:14][CH2:15][O:16][S:61]([CH3:60])(=[O:63])=[O:62])[CH:11]=[C:10]([C:17]2[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=2)[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1424402-(3-Butynyloxy)tetrahydro-2H-pyranHCID 66616455HCID 66616455, compoundHCID 86257326HCID 86257326, compound

Product 2

HCID 57881268HCID 57881268, compoundHCID 86610327HCID 86610327, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step A and B. 2-(2-Benzyl-6-p-tolyl-pyrimidin-4-yl)-ethanol. The title compound was prepared from 2-(3-butynyloxy)tetrahydro-2H-pyran using the methods described in Example 112, Steps A and B. MS (ESI): exact mass calcd. for C20H20N2O, 304.16; m/z found, 305.4 [M+H]+. 1H NMR (CDCl3): 7.98 (d, J=8.2, 2H), 7.42-7.42 (m, 2H), 7.34-7.29 (m, 4H), 7.25-7.22 (m, 1H), 4.31 (s, 2H), 3.98 (t, J=5.3, 2H), 2.97 (t, J=5.3, 2H), 2.42 (s, 3H). Step C. 4-(2-Azido-ethyl)-2-benzyl-6-p-tolyl-pyrimidine. To a 0° C. solution of the product of Step B (0.150 g, 0.493 mmol) in THF (2.5 mL) was added MsCl (0.042 mL, 0.54 mmol) followed by Et3N (0.76 mL, 0.54 mmol). After 1 h, EtOAc was added and the mixture washed with brine, dried and concentrated to give methanesulfonic acid 2-(2-benzyl-6-p-tolyl-pyrimidin-4-yl)-ethyl ester (0.185 g). To a solution of this mesylate (0.120 g, 0.32 mmol) in DMF (1 mL) was added sodium azide (0.105 g, 1.6 mmol). The flask was heated at 40° C. for 10 h, then was cooled to rt, diluted with water, and extracted with EtOAc (3×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (5-15% EtOAc/hexanes) to give 0.080 g (76%) of the title compound. MS (ESI): exact mass calcd. for C20H19N5, 329.16 m/z found, 330.4 [M+H]+. 1H NMR (CDCl3): 7.98 (d, J=8.2, 2H), 7.46-7.43 (m, 2H), 7.38 (s, 1H), 7.32-7.28 (m, 4H), 7.23-7.19 (m, 2H), 4.31 (s, 2H), 3.76 (t, J=6.8, 2H), 3.02 (t, J=6.8, 2H), 2.42 (s, 3H). Step D. To a solution of the product of Step C (0.066 g, 0.2 mmol) in THF (2 mL) was added PPh3 (0.059 g, 2.2 mmol). After 18 h, water was added (0.10 mL) and the mixture was stirred for 48 h. The mixture was diluted with water and extracted with CH2Cl2 (2×). The combined organic layers were dried and concentrated. The resulting residue was purified via SiO2 chromatography (5-15% EtOAc/hexanes) to give 0.060 g (99%) of the title compound. MS (ESI): exact mass calcd. for C20H21N3, 303.17; m/z found, 304.4 [M+H]+. 1H NMR (CDCl3): 7.98-7.96 (m, 2H), 7.45-7.44 (m, 2H), 7.36 (s, 1H), 7.32-7.28 (m, 4H), 7.23-7.19 (m, 1H), 4.31 (s, 2H), 3.13 (t, J=6.5, 2H), 2.91 (t, J=6.5, 2H), 2.42 (s, 3H).

Workup

  1. washthe mixture washed with brine
  2. customdried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-4cf37bb97713465691642e507fda5721
Source dataset
uspto-grants-2009_10
Patent number
US07598255B2

Reaction notes

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