Diisopropylethylamine → tert-Butyl 2-((3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)amino)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate

HRID 604906Notes

Reaction equation

HRID 604906 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10](Br)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][O:17][C:18]1[CH:19]=[C:20]([NH:30][C:31]([NH2:33])=[S:32])[CH:21]=[CH:22][C:23]=1[N:24]1[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]1.C(N(CC)C(C)C)(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:33]=[C:31]([NH:30][C:20]3[CH:21]=[CH:22][C:23]([N:24]4[CH:28]=[C:27]([CH3:29])[N:26]=[CH:25]4)=[C:18]([O:17][CH3:16])[CH:19]=3)[S:32][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 106839701-tert-Butyloxycarbonyl-3-bromo-4-oxopiperidineHCID 71650841[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]thiourea

Product 1

HCID 25106279tert-Butyl 2-((3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)amino)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate

Procedure

The title compound was prepared in analogy to example 1 step e) from 92 mg (0.33 mmol) 3-bromo-4-oxo-piperidine-1-carboxylic acid tert-butyl ester, 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea and 43 mg (0.33 mmol) N,N-diisopropyl ethyl amine. The reaction was poured onto water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated in vacuo. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 99 mg (75%) 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester as a light yellow foam. MS ISP (m/e): 442.3 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.32 (s, 1H), 7.64 (s, 1H), 7.47 (s, 1H), 7.31 (d, 1H), 7.25 (d, 1H), 7.02 (d, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.64 (t, 2H), 2.63 (m, 2H), 2.14 (s, 3H), 1.43 (s, 9H).

Workup

  1. additionThe reaction was poured onto water
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent was evaporated in vacuo
  7. customThe crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 99 mg (75%) 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester as a light yellow foam

Sources & evidence

ORD record
ord-b5a8f8cbe3f74c979ced75dec1c9c5b8
Source dataset
uspto-grants-2011_03
Patent number
US07910740B2

Reaction notes

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