Ammonia → HCID 178461178, compound

HRID 2103726Notes

Reaction equation

HRID 2103726 reaction equation
[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C@H:8]1[CH2:11][C@H:10]([C:12]2[S:13][C:14]3[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[CH:17][C:15]=3[N:16]=2)[CH2:9]1.C(Cl)(=O)C(Cl)=O.C[N:31](C=O)C.N>C(Cl)Cl>[CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C@H:8]1[CH2:11][C@H:10]([C:12]2[S:13][C:14]3[CH:20]=[C:19]([C:21]([NH2:31])=[O:23])[CH:18]=[CH:17][C:15]=3[N:16]=2)[CH2:9]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 178461179HCID 178461179, compound

Product 1

HCID 178461178HCID 178461178, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-{trans-3-[(S)-2-methylpiperidin-1-yl]cyclobutyl}-1,3-benzothiazole-6-carboxylic acid (Example 143B, 20 mg, 0.062 mmol) was added to a solution of oxalyl chloride (17 mg, 0.13 mmol) in CH2Cl2 (1 mL) at 23° C., followed by 1 drop of catalytic amount of DMF. The reaction mixture was allowed to stir for 1 h. Solvent and excess of oxalyl chloride were removed under vacuum, the residue solid was re-dissolved in CH2Cl2 (0.5 mL). Excess of ammonia (2 mL, 1.2 mmol) in CH2Cl2 (2 mL) was then added to the reaction vial. The reaction mixture was then stirred overnight. Solvent was removed, and the crude product was purified via HPLC (C-18 column, 0.1% TFA in acetonitrile) to give 16 mg product as a TFA salt (65%). 1H NMR (500 MHz, CD3OD): δ=8.51 ppm (m, 1H), 8.01 (m, 2H), 4.00 (m, 1H), 3.80 (m, 1H), 3.83 (m, 2H), 2.80-3.15 (m, 5H), 2.74 (m, 1H), 1.94 (m, 3H), 1.75 (m, 3H), 1.41 (m, 3H). MS (ESI, M+H+): 330.0.

Workup

  1. customSolvent and excess of oxalyl chloride were removed under vacuum
  2. dissolutionthe residue solid was re-dissolved in CH2Cl2 (0.5 mL)
  3. stirringThe reaction mixture was then stirred overnight
  4. customSolvent was removed
  5. customthe crude product was purified via HPLC (C-18 column, 0.1% TFA in acetonitrile)

Sources & evidence

ORD record
ord-3e8ac9940a64412089657f7f03f3e105
Source dataset
uspto-grants-2009_08
Patent number
US07576110B2

Reaction notes

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