Diisopropylethylamine → HCID 178461964, compound

HRID 626304Notes

Reaction equation

HRID 626304 reaction equation
[NH2:1][C@@H:2]([C:4]1[O:5][C:6]2[C:11]([C:12](=[O:21])[C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:3].C(N(CC)C(C)C)(C)C.Br[C:32]1[N:40]=[CH:39][N:38]=[C:37]2[C:33]=1[NH:34][CH:35]=[N:36]2>C(O)(C)(C)C>[N:40]1[C:32]([NH:1][C@@H:2]([C:4]2[O:5][C:6]3[C:11]([C:12](=[O:21])[C:13]=2[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH3:3])=[C:33]2[C:37]([NH:36][CH:35]=[N:34]2)=[N:38][CH:39]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5287830Purine, 6-bromo-HCID 117966873HCID 117966873, compound

Product 1

HCID 178461964HCID 178461964, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

This example is also described in Example 56 of WO 2011/055215. To a solution of (R)-2-(1-Amino-ethyl)-3-(3-fluoro-phenyl)-chromen-4-one (0.41 g, 1.52 mmoles) in tert-butanol (7 ml), N,N-diisopropylethylamine (0.53 ml, 3.04 mmoles) and 6-bromopurine (0.242 g, 1.21 mmoles) are added and refluxed for 24 h. The reaction mixture is concentrated, diluted with water, and extracted with ethyl acetate. The organic layer is dried over sodium sulphate and concentrated under reduced pressure. The crude product is purified by column chromatography with methanol:ethyl acetate to afford the title compound as an off-white solid. MP: 274-276° C. 1H-NMR (δ ppm, DMSO-D6, 400 MHz): δ 12.96 (s, 1H), 8.14-8.01 (m, 4H), 8.11 (s, 1H), 7.81 (dt, J=8.5, 1.5 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.49 (m, 2H), 7.25-7.19 (m, 3H), 5.18 (br m, 1H), 1.56 (d, J=7.0 Hz, 3H). Mass: 402.04 (M++1).

Workup

  1. temperaturerefluxed for 24 h
  2. concentrationThe reaction mixture is concentrated
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer is dried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product is purified by column chromatography with methanol

Sources & evidence

ORD record
ord-e0111bc47fe247668bcebcbb6cf9b879
Source dataset
uspto-grants-2016_04
Patent number
US09309216B2

Reaction notes

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