Water → tert-butyl ((1-((3-(2-(dimethylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

HRID 1051029Notes

Reaction equation

HRID 1051029 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[C:13]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])[N:14]([S:16]([C:19]2[CH:20]=[C:21]([CH:27]=[CH:28][CH:29]=2)[O:22][CH2:23][C:24](O)=[O:25])(=[O:18])=[O:17])[CH:15]=1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:50]2[N:51]=[CH:52]C=CC=2N=N1.O>O1CCCC1.C(OCC)(=O)C>[CH3:50][N:51]([CH3:52])[C:24](=[O:25])[CH2:23][O:22][C:21]1[CH:20]=[C:19]([S:16]([N:14]2[C:13]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[F:36])=[CH:12][C:11]([CH2:10][N:8]([CH3:9])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:15]2)(=[O:18])=[O:17])[CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 901689202-(3-((4-(((tert-butoxycarbonyl)(methyl)amino)methyl)-2-(2-fluorophenyl)-1H-pyrrol-1-yl)sulfonyl)phenoxy)acetic acid

Product 1

HCID 90168924tert-butyl ((1-((3-(2-(dimethylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(3-((4-(((tert-Butoxycarbonyl)(methyl)amino)methyl)-2-(2-fluorophenyl)-1H-pyrrol-1-yl)sulfonyl)phenoxy)acetic acid 9b (170 mg, 0.33 mmol) was added to a solution of methylamine in tetrahydrofuran (2 N, 5 mL), followed by addition of 2-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (104 mg, 0.91 mmol) and then the reaction solution was stirred for 3 h. 20 mL of water and 20 mL of ethyl acetate were added, and the reaction solution was layered, the water phase was extracted with ethyl acetate (20 mL×1). The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by thin layer chromatography with elution system C to obtain the title product tert-butyl ((1-((3-(2-(dimethylamino)-2-oxoethoxy)phenyl)sulfonyl)-5-(2-fluorophenyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 9c (50 mg, a white solid) in 28% yield.

Workup

  1. extractionthe water phase was extracted with ethyl acetate (20 mL×1)
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by thin layer chromatography with elution system C

Sources & evidence

ORD record
ord-e2e15dc5e63d48f5a0b9f99447cc4d33
Source dataset
uspto-grants-2016_07
Patent number
US09388133B2

Reaction notes

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