Methylamine → HCID 89691388, compound

HRID 1054193Notes

Reaction equation

HRID 1054193 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].F[P-](F)(F)(F)(F)F.[N:31]1(OC(N(C)C)=[N+](C)C)[C:35]2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN>CN(C)C=O.C(OCC)(=O)C>[CH3:35][NH:31][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 (SM2-A, 10 g, 32 mmol) in dimethylformamide (DMF, 100 ml) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 15.5 g, 42 mmol), followed by diisopropylethylamine (DIEA, 12.4 g, 96 mmol) while the temperature was maintained below 0° C. After stirring at this temperature for 2 hours (h), methylamine (32 mL, 63 mmol, 2 M in THF) was added. The reaction mixture was warmed to rt and stirred at rt for 16 h. The solution was diluted with ethyl acetate (500 mL); washed with water (200 mL), 0.1 M of hydrochloride (100 mL), saturated NaHCO3 (100 mL), and then brine (100 mL); dried over Na2SO4; and concentrated and purified by column chromatograph (CC, dichloromethane (DCM): MeOH=200:1) to give product (4-A) (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 of hydrochloride (100 mL), saturated NaHCO3 (100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationand concentrated
  6. custompurified by column chromatograph (CC, dichloromethane (DCM): MeOH=200:1)

Sources & evidence

ORD record
ord-09cc01b0401f4ae09ed091b87cfae6c1
Source dataset
uspto-grants-2016_07
Patent number
US09394296B2

Reaction notes

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