Triethylamine → HCID 86705965, compound

HRID 1408173Notes

Reaction equation

HRID 1408173 reaction equation
[CH3:1][N:2]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[C:3](=[O:45])[C:4]1[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][C:11]=2[C:22]2[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[CH:25]=[CH:24][N:23]=2)=[O:8])[CH:5]=1.C(N(CC)CC)C.[CH3:61][S:62](Cl)(=[O:64])=[O:63]>ClCCl>[CH3:1][N:2]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][N:51]([S:62]([CH3:61])(=[O:64])=[O:63])[CH2:50][CH2:49]1)[C:3](=[O:45])[C:4]1[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][C:11]=2[C:22]2[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:40])[F:38])[CH:32]=3)[CH:25]=[CH:24][N:23]=2)=[O:8])[CH:5]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66588053HCID 66588053, compound

Product 1

HCID 86705965HCID 86705965, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of N1-methyl-N1-(2-(piperazin-1-yl)ethyl)-N3-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide (100 mg, 0.14 mmol, 1.00 equiv) in dichloromethane (3 mL), triethylamine (42 mg, 0.42 mmol, 3.00 equiv), and methanesulfonyl chloride (17 mg, 0.15 mmol, 1.05 equiv). The resulting solution was stirred for 40 min at 25° C. The reaction was then quenched by the addition of 3 mL of water. The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×5 mL of water and 1×5 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (90 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 55.8 mg (50%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.97 (d, J=5.1 Hz, 1H), 8.764 (d, J=9.0 Hz, 1H), 8.45 (s, 1H), 8.16˜8.10 (m, 3H), 7.89˜7.87 (m, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.72˜7.67 (m, 4H), 7.62˜7.53 (m, 2H), 4.72 (s, 2H), 4.00 (s, 2H), 3.68˜3.55 (m, 14H), 3.11 (s, 3H), 2.96 (s, 3H), 2.04 (d, J=4.8 Hz, 1H), 1.83 (d, J=5.1 Hz, 1H). MS (ES, m/z): 806 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. customThe reaction was then quenched by the addition of 3 mL of water
  3. extractionThe resulting solution was extracted with 2×5 mL of dichloromethane
  4. washThe resulting mixture was washed with 1×5 mL of water and 1×5 mL of brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product (90 mg) was purified by reverse phase HPLC
  8. washeluting with a water/CH3CN gradient
  9. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-8af57a8a293b43859d4cd295f5fd23ad
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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