Ammonia → HCID 178461178, compound

HRID 2047572Notes

Reaction equation

HRID 2047572 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-de7e184e4d2b45d493114268d58f105d
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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