Trimethylsilyl triflate → HCID 66760128, compound

HRID 889191Notes

Reaction equation

HRID 889191 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][O:9][C:10]2[C:18]3[N:17]=[C:16]([O:19][CH3:20])[N:15]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:14]=3[CH:13]=[CH:12][CH:11]=2)=[C:6]([Cl:28])[CH:5]=[CH:4][C:3]=1[N:29]([CH3:53])[C:30](=[O:52])[CH2:31][NH:32][C:33]([CH:35]1[CH2:39][CH2:38][N:37]([CH:40]2[CH2:44][CH2:43][N:42](C(OC(C)(C)C)=O)[CH2:41]2)[CH2:36]1)=[O:34].O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>ClCCl>[Cl:1][C:2]1[C:7]([CH2:8][O:9][C:10]2[C:18]3[N:17]=[C:16]([O:19][CH3:20])[N:15]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:14]=3[CH:13]=[CH:12][CH:11]=2)=[C:6]([Cl:28])[CH:5]=[CH:4][C:3]=1[N:29]([CH3:53])[C:30](=[O:52])[CH2:31][NH:32][C:33]([CH:35]1[CH2:39][CH2:38][N:37]([CH:40]2[CH2:44][CH2:43][NH:42][CH2:41]2)[CH2:36]1)=[O:34]

Participants

4

Reactant 2

HCID 65367Trimethylsilyl triflate2×HCID 66760636HCID 66760636, compound

Product 1

HCID 66760128HCID 66760128, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 3-((2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)carbamoyl)-[1,3′-bipyrrolidine]-1′-carboxylate (0.27 g, 0.35 mmol) in dichloromethane (10 ml) was cooled in an ice bath and treated with dropwise addition of trimethylsilyl triflate (0.07 mL, 0.39 mmol) and stirred at 0° C. for ten minutes. The reaction was treated with another dropwise addition of trimethylsilyl triflate (0.06 mL, 0.35 mmol) stirring at 0° C. for one hour. The reaction was quenched with triethyl amine (1 mL), evaporated, treated with aqueous saturated sodium bicarbonate (10 mL) and brine (100 mL) and extracted with dichloromethane (100 mL×3). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to afford N-(2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)-[1,3′-bipyrrolidine]-3-carboxamide (22) as a tan solid, 0.22 g (94%), that was about 90% pure by LC/MS (+ESI) m/z 666 (M++1) with about 10% impurity of MW 786 (M+). 786 (M++1). 1HNMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.93 (m, 1H), 7.59 (m, 1H), 7.45 (m, 1H), 7.32 (m, 1H), 7.19 (m, 1H), 7.04 (m, 1H), 6.95 to 2.00 (many m, 17H). 13CNMR (100 MHz, CDCl3) δ 175.6, 169.5, 169.2, 156.9, 156.1, 149.6, 149.1, 138.4, 137.1, 136.4, 135.8, 135.4, 130.1, 129.8, 122.6, 121.7, 120.8, 107.4, 103.1, 67.1, 62.6, 57.5, 55.0, 54.9, 53.4, 51.4, 50.4, 47.7, 46.1, 44.0, 43.9, 41.9, 30.9, 9.0.

Workup

  1. stirringstirring at 0° C. for one hour
  2. customThe reaction was quenched with triethyl amine (1 mL)
  3. customevaporated
  4. additiontreated with aqueous saturated sodium bicarbonate (10 mL) and brine (100 mL)
  5. extractionextracted with dichloromethane (100 mL×3)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-e138a08e44ae49d19767d4d522d296b7
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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