Hydrochloric Acid → HCID 56595705, compound

HRID 1663400Notes

Reaction equation

HRID 1663400 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@H:15]([C:16]([CH3:21])([CH3:20])[C:17](O)=[O:18])[C:5]2=[CH:4][CH:3]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3.C(N(CC)CC)C.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[S:53]1[CH:57]=[N:56][N:55]=[C:54]1[NH2:58].Cl>C(#N)C.CCO>[Cl:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@H:15]([C:16]([CH3:21])([CH3:20])[C:17]([NH:58][C:54]4[S:53][CH:57]=[N:56][N:55]=4)=[O:18])[C:5]2=[CH:4][CH:3]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 199091,3,4-Thiadiazol-2-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56594521HCID 56594521, compound

Product 1

HCID 56595705HCID 56595705, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a soln. of (S)-2-(2-chloro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid (30b, 10 g, 32.9 mmol) in acetonitrile (200 ml) was added triethylamine (22.94 ml, 165 mmol), O-(7-AZABENZOTRIAZOL-1-YL)-N,N,N′,N′-TETRAMETHYLURONIUM PF6 (HATU) (16.27 g, 42.8 mmol) and 1,3,4-thiadiazol-2-amine (9.99 g, 99 mmol). The resulted mixture was heated at 80° C. for 12 h. The reaction mixture was then concentrated in vacuum and the residue was partitioned between EtOAc and 1N HCl. The obtained organic layer was washed with saturated NaHCO3, brine, then dried (Na2SO4) and concentrated to give a solid. The solid was dissolved in EtOH (400 mL) with gentle warming. Added 1N HCl (˜200 mL) portionwise. The solid was collected and washed with water, dried on vacuum pump overnight to give 10 g (79%) of (S)-2-(2-chloro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methyl-N-(1,3,4-thiadiazol-2-yl)propanamide (53a). MS (E+) m/z: 387 (M+H); LC retention time: 3.12 min.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuum
  2. customthe residue was partitioned between EtOAc and 1N HCl
  3. washThe obtained organic layer was washed with saturated NaHCO3, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give a solid
  7. customThe solid was collected
  8. washwashed with water
  9. customdried on vacuum pump overnight

Sources & evidence

ORD record
ord-55aa90e4147440599ff977c820a30fe7
Source dataset
uspto-grants-2011_10
Patent number
US08034940B2

Reaction notes

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