Triethylamine → HCID 68708584, compound

HRID 2261917Notes

Reaction equation

HRID 2261917 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]([CH3:20])([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:10]=[N:11][OH:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][N:22]([C:27]1[CH:28]=[C:29]([CH:42]=[C:43]([C:45]#[CH:46])[CH:44]=1)[C:30]([NH:32][C@@H:33]([C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)[CH3:34])=[O:31])[S:23]([CH3:26])(=[O:25])=[O:24].C(N(CC)CC)C>CN(C=O)C>[CH3:21][N:22]([C:27]1[CH:28]=[C:29]([CH:42]=[C:43]([C:45]2[O:12][N:11]=[C:10]([C@@:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])([CH3:20])[CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:46]=2)[CH:44]=1)[C:30]([NH:32][C@@H:33]([C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)[CH3:34])=[O:31])[S:23]([CH3:26])(=[O:25])=[O:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 86615676HCID 86615676, compound2×HCID 86615681HCID 86615681, compound2×

Product 1

HCID 68708584HCID 68708584, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
5 °C

Procedure

To a solution of (R)-2-tert-butoxycarbonylamino-2-methyl-3-phenylpropanal oxime (Intermediate L, 30 mg, 0.11 mmol) in 0.5 mL DMF, cooled to 5° C., was added a solution of N-bromosuccinimide from Step B (29 mg, 0.165 mmol) in 0.5 mL DMF dropwise. After stirring at 5° C. for 1 h, a solution of 3-(N-methyl-N-(methylsulfonyl)amino)-5-ethynyl-N—((R)-1-(4-fluorophenyl)ethyl)benzamide (124 mg, 0.33 mmol) and triethylamine (0.023 mL, 0.165 mmol) in 0.2 mL DMF was added. The reaction was stirred at rt for 1 week and then heated to 50° C. overnight. Purification by reverse phase preparative HPLC (5-95% CH3CN in water containing 0.1% TFA) gave 3-(N-methyl-N-(methylsulfonyl)amino)-5-(3-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)isoxazol-5-yl)-N—((R)-1-(4-fluorophenyl)ethyl)benzamide. 1H NMR (CDCl3) δ 8.02 (s, 1H), 7.90 (m, 1H), 7.86 (m, 1H), 7.38 (m, 2H), 7.26 (m, 3H), 7.08 (m, 4H), 6.60 (s, 1H), 6.44 (d, J=7.6 Hz, 1H), 5.31 (m, 1H), 5.01 (bs, 1H), 3.53 (d, J=12.9 Hz, 1H), 3.39 (s, 3H), 3.34 (m, 1H), 2.89 (s, 3H), 1.63 (m, 6H), 1.44 (s, 9H).

Workup

  1. stirringThe reaction was stirred at rt for 1 week
  2. temperatureheated to 50° C. overnight
  3. customPurification by reverse phase preparative HPLC (5-95% CH3CN in water containing 0.1% TFA)

Sources & evidence

ORD record
ord-53f8d2557f074258bb65421c76d3f931
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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