Triethylamine → HCID 90467012, compound

HRID 1753252Notes

Reaction equation

HRID 1753252 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=3)[C:12]([C:20]([OH:22])=O)=[CH:11]2)[C:4]=1[CH3:23].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[NH2:49][CH2:50][C@H:51]([OH:53])[CH3:52]>C(Cl)Cl>[OH:53][C@H:51]([CH3:52])[CH2:50][NH:49][C:20]([C:12]1[C:13]2=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=[C:18]2[N:10]([CH2:9][C:5]2[C:4]([CH3:23])=[C:3]([O:2][CH3:1])[N:8]=[CH:7][N:6]=2)[CH:11]=1)=[O:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 439938(2R)-1-aminopropan-2-olHCID 117819025HCID 117819025, compound

Product 1

HCID 90467012HCID 90467012, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

See FIG. 23(c). 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (75 mg, 0.24 mmol) was taken in a thermal reactor. DCM (5 mL) was added to get a suspension. Added triethyl amine (0.067 mL, 0.48 mmol) followed by the addition of 1-Propanephosphonic acid cyclic anhydride (0.286 mL, 0.48 mmol). (R)-1-aminopropan-2-ol (36.1 mg, 0.48 mmol) was added and stirred at RT for ON. After completion of the reaction, reaction mixture was concentrated and dissolved in DCM:MeOH. This crude compound was subjected for reverse phase purification to obtain (R)—N-(2-hydroxypropyl)-1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (35.0 mg, 39.5%) as a off-white solid. ES+MS m/z: 370 (M+I). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.10 (d, J=5.84 Hz, 3 H ) 2.24 (s, 3 H ) 2.39 (s, 3 H ) 3.16-3.29 (m, 1 H ) 3.37-3.48 (m, 1 H ) 3.77 (br. s., 1H ) 3.93 (s, 3 H ) 4.85 (d, J=4.33 Hz, 1 H ) 5.63 (s, 2 H ) 7.74 (s, 1 H ) 8.12 (s, 1 H ) 8.33 (s, 1 H ) 8.41 (s, 1 H ) 8.82 (br. s., 1 H ).

Workup

  1. customto get a suspension
  2. customAfter completion of the reaction, reaction mixture
  3. concentrationwas concentrated
  4. dissolutiondissolved in DCM
  5. customThis crude compound was subjected for reverse phase purification

Sources & evidence

ORD record
ord-61566ddc6ac74627acf8e6ecf9056efa
Source dataset
uspto-grants-2015_10
Patent number
US09163020B2

Reaction notes

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