Methylamine → HCID 89691388, compound

HRID 1054197Notes

Reaction equation

HRID 1054197 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:20]([C:21]([OH:23])=O)[CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][N:25](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN>CN(C=O)C.C(OCC)(=O)C>[CH3:24][NH:25][C:21]([C@@H:20]1[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[CH2:19]1)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[O:23]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 1268156HCID 1268156, compoundHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 89691388HCID 89691388, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-2-(tert-butoxycarbonyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid (SM1-B, 10 g, 32 mmol) in DMF (100 ml) was added HATU (15.5 g, 42 mmol), followed by DIEA (12.4 g, 96 mmol) while the temperature was maintained below 0° C. After stirring for 2 h at this temperature, methylamine (2M in THF, 32 mL, 63 mmol) was added. The reaction mixture was warmed to rt and stirred for 16 h. The solution was diluted with ethyl acetate (500 mL); washed with water (200 mL), 0.1 M hydrochloride (100 mL), saturated NaHCO3 (100 mL), and brine (100 mL); dried over Na2SO4; and concentrated and purified by column chromatography (DCM:MeOH=200:1) to give product (2-B) (10 g, 96%) as a white solid. LC-MS (M+H)+=330.

Workup

  1. temperaturewas maintained below 0° C
  2. additionwas added
  3. washwashed with water (200 mL), 0.1 M hydrochloride (100 mL), saturated NaHCO3 (100 mL), and brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationand concentrated
  6. custompurified by column chromatography (DCM:MeOH=200:1)

Sources & evidence

ORD record
ord-aa26cc909506466bb210f6965bff0173
Source dataset
uspto-grants-2016_07
Patent number
US09394296B2

Reaction notes

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