Diisopropylethylamine → HCID 66698055, compound

HRID 516304Notes

Reaction equation

HRID 516304 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[C:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:33]([F:35])[F:34])[N:3]=1.[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)(=[O:39])=[O:38].CCN(C(C)C)C(C)C>C1COCC1>[F:35][CH:33]([F:34])[C:15]1[N:14]([C:4]2[N:3]=[C:2]([N:43]3[CH2:44][CH2:45][N:40]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:41][CH2:42]3)[N:7]=[C:6]([N:8]3[CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[N:5]=2)[C:18]2[CH:19]=[C:20]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:31])[CH3:30])[CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 86645852tert-butyl 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate

Product 1

HCID 66698055HCID 66698055, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of tert-butyl 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate (0.333 g, 0.65 mmol), 1-(methylsulfonyl)piperazine (0.32 g, 2 mmol), and DIPEA (0.17 g, 1.3 mmol) in THF (50 mL) was heated under reflux for 3 hrs. The solution was concentrated and then diluted with 100 mL of water containing 1% HOAc to give a solid, which was collected and dried. Chromatography on silica eluting with CH2Cl2/EtOAc (4:1), followed by recrystallization from MeOH, gave 0.33 g (79% yield) of tert-butyl 2-(difluoromethyl)-4-methoxy-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-6-ylcarbamate: mp 223° C. (decomp.); 1H NMR (CDCl3) δ 8.63 (br s, 1H), 7.44 (t, JHF=53.6 Hz, 1H), 6.62 (br s, exchangeable with D2O, 1H), 6.35 (d, J=1.7 Hz, 1H), 4.09-3.80 (m, 15H), 3.35 (m, 4H), 2.80 (s, 3H), 1.52 (s, 9H); Anal. Calcd. for C26H35F2N9O6S: C, 48.8; H, 5.5; N, 19.7. Found: C, 48.9; H, 5.6; N, 19.9%.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 hrs
  3. concentrationThe solution was concentrated
  4. additiondiluted with 100 mL of water containing 1% HOAc
  5. customto give a solid, which
  6. customwas collected
  7. customdried
  8. customChromatography on silica eluting with CH2Cl2/EtOAc (4:1), followed by recrystallization from MeOH

Sources & evidence

ORD record
ord-43411d3268874f5fb80df3c57a9ac2ab
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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