Morpholine → 4-(morpholin-4-yl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

HRID 1750282Notes

Reaction equation

HRID 1750282 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[N:13][N:14]([CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][O:17]4)[CH:15]=3)=[CH:9][N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:4]=2[N:5]=[CH:6][N:7]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C(N(CC)C(C)C)(C)C>C(O)CCC>[N:30]1([C:2]2[C:3]3[C:10]([C:11]4[CH:12]=[N:13][N:14]([CH:16]5[CH2:21][CH2:20][CH2:19][CH2:18][O:17]5)[CH:15]=4)=[CH:9][N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:29])[CH3:27])[C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 867069554-chloro-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867069564-(morpholin-4-yl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 4-chloro-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (C18) (3.3 g, 7.6 mmol), morpholine (0.99 g, 11 mmol) and N,N-diisopropylethylamine (6 mL, 34 mmol) in n-butanol (15 mL) was irradiated in a microwave synthesizer at 100° C. for 30 minutes. After removal of solvents in vacuo, the residue was purified by silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether) to provide the product as a brown oil. Yield: 2.6 g, 5.4 mmol, 71%. 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 7.79 (s, 1H), 7.71 (s, 1H), 7.17 (s, 1H), 5.62 (s, 2H), 5.44 (dd, J=6.5, 6.0 Hz, 1H), 4.08-4.15 (m, 1H), 3.71-3.79 (m, 1H), 3.62-3.67 (m, 4H), 3.58 (dd, J=8.5, 8.0 Hz, 2H), 3.33-3.39 (m, 4H), 2.06-2.19 (m, 3H), 1.62-1.79 (m, 3H), 0.93 (dd, J=8.5, 7.5 Hz, 2H), −0.04 (s, 9H).

Workup

  1. customAfter removal of solvents in vacuo
  2. customthe residue was purified by silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-a1ff6228051f4fb09583c9b1f988e4f2
Source dataset
uspto-grants-2015_10
Patent number
US09156845B2

Reaction notes

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