N-(tert-butoxycarbonyl)glycine → tert-butyl {2-[(3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)-pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)amino]-2-oxoethyl}carbamate

HRID 1783814Notes

Reaction equation

HRID 1783814 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([S:29]([C:32]5[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=5)(=[O:31])=[O:30])[CH2:24]4)[N:17]=2)[CH:13]=[CH:12][S:11]3)[CH:5]=[CH:6][CH:7]=1.[C:39]([O:43][C:44]([NH:46][CH2:47][C:48](O)=[O:49])=[O:45])([CH3:42])([CH3:41])[CH3:40].CCN(C(C)C)C(C)C.[Cl-].ClC1N(C)C=C[N+]=1C>C(Cl)Cl>[C:39]([O:43][C:44](=[O:45])[NH:46][CH2:47][C:48]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([S:29]([C:32]5[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=5)(=[O:31])=[O:30])[CH2:24]4)[N:17]=2)[CH:13]=[CH:12][S:11]3)[CH:3]=1)=[O:49])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 111266512-chloro-1,3-dimethyl-1H-imidazol-3-ium chlorideHCID 574631524-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}pyrimidin-2-amine

Product 1

HCID 57590777tert-butyl {2-[(3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)-pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)amino]-2-oxoethyl}carbamateYield 55.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 4-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)-sulfonyl]piperidin-3-yl}pyrimidin-2-amine (0.1 g, 0.177 mmol) and N-(tert-butoxycarbonyl)glycine (34 mg, 0.194 mmol) were dissolved in DCM (5 ml) and treated with Hunig's base (92 uL, 0.53 mmol) and 2-chloro-1,3-dimethyl-1H-imidazol-3-ium chloride (33 mg, 0.194 mmol). The mixture was kept at room temperature for 90 minutes then was diluted with DCM (10 ml). The organic phase was washed with water (2×10 ml) and with an aqueous sodium chloride solution (10 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow oil. The product was purified by flash chromatography (gradient 70%-100% EtOAc/hexanes), affording the title compound as a pale yellow solid (71 mg). 400 MHz 1H NMR (DMSO-d6) δ: 9.86 (s, 1H), 8.73 (br. s, 1H), 8.11 (d, J=5.5 Hz, 1H), 7.84 (s, 1H), 7.79-7.75 (m, 2H), 7.70-7.65 (m, 3H), 7.45-7.37 (m, 2H), 7.26 (d, J=7.4 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 6.82 (br. s, 1H), 6.42 (d, J=6.9 Hz, 1H), 4.00-3.90 (m, 1H), 3.78-3.70 (m, 3H), 3.52-3.44 (m, 1H), 3.18 (s, 2H), 2.34 (t, J=10.2 Hz, 1H), 1.94-1.81 (m, 2H), 1.65-1.52 (m, 1H), 1.39 (s, 9H). LCMS: 723 [M+H].

Workup

  1. washThe organic phase was washed with water (2×10 ml) and with an aqueous sodium chloride solution (10 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customgiving a yellow oil
  5. customThe product was purified by flash chromatography (gradient 70%-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bc6414b4a673402f8deae24fb908797d
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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