3-Pyridinemethanol → HCID 136348423, compound

HRID 1748724Notes

Reaction equation

HRID 1748724 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:25])[CH:5]=[CH:6][C:7]=1[CH:8]1[S:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]([CH3:24])[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:9]1=2.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32]O)[CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:24][N:15]1[C:10]2[NH:11][CH2:12][CH2:13][S:14][CH:8]([C:7]3[CH:6]=[CH:5][C:4]([O:25][CH2:32][C:28]4[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=4)=[CH:3][C:2]=3[CH3:1])[C:9]=2[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:16]1

Participants

6

Reactant 4

HCID 75103-PyridinemethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 136216238HCID 136216238, compound

Product 1

HCID 136348423HCID 136348423, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a degassed solution of 3-methyl-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]phenol (0.071 g, 0.2 mmol, Ex. #D.42) in anhydrous THF (10 mL) was added 3-pyridinemethanol (0.033 g, 0.3 mmol) and triphenylphosphine (0.131 g, 0.5 mmol), at rt. After 30 min the mixture was cooled to about 0° C. and diisopropyl azodicarboxylate (0.1 mL, 0.5 mmol) was added dropwise. The resulting mixture was stirred for about 16 h at rt, and then concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/methanol 95:5) followed by trituration with diethyl ether to give 1-methyl-4-[2-methyl-4-(3-pyridylmethoxy)phenyl]-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.012 g, 0.03 mmol, 14%) as a pale yellow solid: LC-MS (Table 1, Method e) Rt=5.09 min; m/z 444 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.59 (3 H, s) 2.70 (1 H, ddd, J=14.9, 6.1, 2.3 Hz) 2.88 (1 H, ddd, J=14.9, 8.8, 2.5 Hz) 3.19-3.29 (1 H, m) 3.53-3.62 (1 H, m) 3.78 (1 H, br s) 3.84 (3 H, s) 5.01 (2 H, s) 6.62 (1 H, s) 6.63 (1 H, dd, J=8.4, 2.6 Hz) 6.82 (1 H, d, J=2.6 Hz) 7.07 (1 H, ddd, J=7.4, 4.9, 1.2 Hz) 7.16 (1 H, d, J=8.4 Hz) 7.30 (1 H, dd, J=7.8, 4.9 Hz) 7.58 (1 H, td, J=7.8, 1.9 Hz) 7.71-7.79 (2 H, m) 8.48 (1 H, d, J=4.9 Hz) 8.56 (1 H, dd, J=4.8, 1.5 Hz) 8.65 (1 H, d, J=1.9 Hz).

Workup

  1. customat rt
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography (SiO2, ethyl acetate/methanol 95:5)

Sources & evidence

ORD record
ord-b0cbaaf1205a4deab1e1c153f423a16e
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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