Triethylamine → HCID 71543069, compound

HRID 931647Notes

Reaction equation

HRID 931647 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([F:10])[C:7]3[O:11][C:12]4[C:17]([C@@:18]5([CH2:23][CH2:22][O:21][C:20]([NH2:24])=[N:19]5)[C:6]=3[CH:5]=2)=[CH:16][C:15]([NH2:25])=[CH:14][CH:13]=4)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([C:33](O)=[O:34])=[N:31][CH:32]=1.C(N(CC)CC)C.CCCP(=O)=O>CCOC(C)=O>[NH2:24][C:20]1[O:21][CH2:22][CH2:23][C@:18]2([C:6]3[CH:5]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[N:9]=[C:8]([F:10])[C:7]=3[O:11][C:12]3[C:17]2=[CH:16][C:15]([NH:25][C:33](=[O:34])[C:30]2[CH:29]=[CH:28][C:27]([Cl:26])=[CH:32][N:31]=2)=[CH:14][CH:13]=3)[N:19]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27628725-Chloro-2-picolinic acidHCID 16167369Propylphosphoric anhydrideHCID 117600300HCID 117600300, compound

Product 1

HCID 71543069HCID 71543069, compoundYield 12.31%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (S)-3-cyclopropyl-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.0864 g, 0.254 mmol) and 5-chloro-2-pyridinecarboxylic acid (0.044 g, 0.279 mmol) in EtOAc (2 mL) was added triethylamine (0.106 ml, 0.762 mmol). The mixture was stirred for one minute and propylphosphonic anhydride solution, 50 wt. % in ethyl acetate (0.302 ml, 0.508 mmol) was added. Stirring continued for 1 h. The reaction was quenched with saturated NaHCO3 and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-5% MeOH/DCM and repurified by HPLC to afford (S)—N-(2′-amino-3-cyclopropyl-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-chloropicolinamide as a white solid (0.015 g, 0.031 mmol, 12.31% yield). MS m/z=480.0 [M+H]+.

Workup

  1. stirringStirring
  2. waitcontinued for 1 h
  3. customThe reaction was quenched with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on silica gel using 0-5% MeOH/DCM
  9. customrepurified by HPLC

Sources & evidence

ORD record
ord-2f2d8eab7b494bbc95345df4a492b13e
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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