Methylamine → HCID 24957241, compound

HRID 244433Notes

Reaction equation

HRID 244433 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[N:25]=[CH:24]4)([OH:20])[C:16]([F:19])([F:18])[F:17])=[CH:7][N:8]2[CH2:11][C:12](O)=[O:13])=[CH:4][CH:3]=1.[CH2:37]([N:39](CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.CN>CN(C=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]([C:21]3[CH:22]=[C:23]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[N:25]=[CH:24]4)([OH:20])[C:16]([F:17])([F:19])[F:18])=[CH:7][N:8]2[CH2:11][C:12]([NH:39][CH3:37])=[O:13])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 2724699PyBOPHCID 59437322HCID 59437322, compound

Product 1

HCID 24957241HCID 24957241, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a room temperature solution of 135 mg (0.24 mmol) of (6-bromo-3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}indol-1-yl)acetic acid in 1 mL of DMF was added 121 mg (1.2 mmol) of triethylamine followed by 210 mg (0.40 mmol) of benzotriazole-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP). After 5 minutes, 162 mg (2.4 mmol) of methyl amine was added. The mixture stirred overnight and was filtered and purified by HPLC using CH3CN-water buffered with 0.1% TFA (5-90% gradient). The material from the column was concentrated to remove CH3CN. The resulting aqueous portion was extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo to afford 20.0 mg (15%) of the title compound. LCMS [M+H]=576.35.

Workup

  1. filtrationwas filtered
  2. custompurified by HPLC
  3. concentrationThe material from the column was concentrated
  4. customto remove CH3CN
  5. extractionThe resulting aqueous portion was extracted with ethyl acetate
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f2ce5833753347bb8f0787077708c7dc
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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