Triethylamine → HCID 68181680, compound

HRID 1398628Notes

Reaction equation

HRID 1398628 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C@@:19]([OH:27])([C:21]4[N:25]=[C:24]([CH3:26])[O:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:28](O)=[O:29])=[N:9]2)[C:5]([Cl:31])=[CH:4][N:3]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[NH:57]1[CH2:60][CH:59]([OH:61])[CH2:58]1.C(N(CC)CC)C>CN(C=O)C.O.C(#N)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C@@:19]([OH:27])([C:21]4[N:25]=[C:24]([CH3:26])[O:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:28]([N:57]3[CH2:60][CH:59]([OH:61])[CH2:58]3)=[O:29])=[N:9]2)[C:5]([Cl:31])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 27592903-Hydroxyazetidine hydrochloride2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 68181829HCID 68181829, compound

Product 1

HCID 68181680HCID 68181680, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-(2-amino-5-chloropyrimidin-4-yl)-6-[(3R)-3-hydroxy-3-(5-methyl-1,2,4-oxadiazol-3-yl)but-1-yn-1-yl]-1H-indazole-3-carboxylic acid (100 mg at 65% purity, 0.14 mmol) in DMF (3 mL) was introduced O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (105 mg, 0.28 mmol), azetidin-3-ol hydrochloride (30 mg, 0.28 mmol) and triethylamine (0.06 mL, 0.42 mmol). After 5 hr at RT, the reaction mixture was retreated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (105 mg, 0.28 mmol), azetidin-3-ol hydrochloride (30 mg, 0.28 mmol) and triethylamine (0.06 mL, 0.42 mmol). The reaction was given a further 1 hr at RT, then diluted with water (2 ml) and extracted with EtOAc (2×5 mL extractions). The combined organic extracts were washed with water (5 mL) and brine (5 ml), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by silica gel flash column chromatography (DCM containing a 2-12% gradient of methanol) furnished a solid which was suspended in acetonitrile (2 mL). Filtration furnished the title compound as a colorless solid: 1H NMR (500 MHz, DMSO-d6) delta 1.86 (3H, s), 2.62 (3H, s), 3.85 (1H, dd, J=10.9, 4.1 Hz), 4.19-4.45 (2H, m), 4.45-4.67 (1H, m), 4.71-4.97 (1H, m), 5.80 (1H, s), 6.76 (1H, s), 7.26-7.58 (3H, m), 8.02-8.35 (2H, m), 8.54 (1H, s); LC-MS: m/z=+495.05/497.10 (M+H)+.

Workup

  1. waitThe reaction was given a further 1 hr at RT
  2. extractionextracted with EtOAc (2×5 mL extractions)
  3. washThe combined organic extracts were washed with water (5 mL) and brine (5 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by silica gel flash column chromatography (DCM containing a 2-12% gradient of methanol)
  8. customfurnished a solid which
  9. filtrationFiltration

Sources & evidence

ORD record
ord-cded8105594a4b02a58a3bed462aba3f
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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