Triethylamine → HCID 89473223, compound

HRID 931652Notes

Reaction equation

HRID 931652 reaction equation
[F:1][C:2]1[C:15]2[O:14][C:13]3[C:8](=[CH:9][C:10]([NH2:16])=[CH:11][CH:12]=3)[C@@:7]3([CH2:21][CH2:20][O:19][C:18]([NH2:22])=[N:17]3)[C:6]=2[CH:5]=[C:4]([O:23][CH3:24])[CH:3]=1.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([C:32](O)=[O:33])=[N:30][CH:31]=1.C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(OCC)(=O)C>[NH2:22][C:18]1[O:19][CH2:20][CH2:21][C@@:7]2([N:17]=1)[C:6]1[CH:5]=[C:4]([O:23][CH3:24])[CH:3]=[C:2]([F:1])[C:15]=1[O:14][C:13]1[C:8]2=[CH:9][C:10]([NH:16][C:32](=[O:33])[C:29]2[CH:28]=[CH:27][C:26]([Cl:25])=[CH:31][N:30]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 27628725-Chloro-2-picolinic acidHCID 117600153HCID 117600153, compound

Product 1

HCID 89473223HCID 89473223, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (S)-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthene]-2,7′-diamine (102 mg, 0.310 mmol) and 5-chloropicolinic acid (54 mg, 0.341 mmol) in ethyl acetate (2 mL) was added triethylamine (0.13 mL, 0.929 mmol) and the mixture was stirred for 2 min, followed by addition of 1-propanephosphonic acid cyclic anhydride (T3P) (50 wt. % solution in ethyl acetate) (0.37 mL, 0.619 mmol). After 2 hr at RT, the mixture was quenched with sat NaHCO3 and diluted with 3 ml EtOAc. The organic layer was separated, concentrated in vacuo, and the residue purified by FC on 12 g RediSep Gold column using 10-80% DCM/MeOH/NH4OH (90:10:1) in DCM to afford (S)—N-(2-amino-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl)-5-chloropicolinamide (68 mg, 0.145 mmol, 47% yield).

Workup

  1. waitAfter 2 hr at RT
  2. customthe mixture was quenched with sat NaHCO3
  3. additiondiluted with 3 ml EtOAc
  4. customThe organic layer was separated
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by FC on 12 g RediSep Gold column

Sources & evidence

ORD record
ord-3b3fe7177917479c9e887d1af15dcd3d
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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