Triethylamine → HCID 21882279, compound

HRID 1975964Notes

Reaction equation

HRID 1975964 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClS([N:36]=[C:37]=O)(=O)=O.ClS([NH-])(=O)=O.CCN(CC)CC>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[C:12]2[C:37]#[N:36])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 70918Chlorosulfonyl isocyanateHCID 21882255HCID 21882255, compoundHCID 86588665HCID 86588665, compound

Product 1

HCID 21882279HCID 21882279, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

In a reaction flask 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1H-indole No. 141 (5.90 g, 14.6 mmol) was mixed with CH2Cl2 (90 mL) was cooled down to 0° C. (the starting material did not completely dissolve in CH2Cl2). While stirring vigorously, a solution of chlorosulfonyl isocyanate (2.26 g, 16.0 mmol) in CH2Cl2 (25 mL) was added dropwise over a period of 45 min. The reaction was run at 0° C. for 2 hrs while detected by TLC for the formation of the insoluble N-chlorosulfonylamide intermediate. After this period, Et3N (1.47 g, 14.6 mL) in CH2Cl2 (25 mL) was added dropwise over 45 min at 0° C. The insoluble residue became soluble in the reaction solvent as the Et3N addition was approaching completion. The reaction was let go for the additional 1 hr at 0° C. and 2 hrs at rt. The progress of the reaction could be observed by the insoluble solid formation of the product as the reaction time went on. The solvent was stripped down and the solid residue purified by trituration with methanol to yield (4.0 g, 63.8%). Mp=238-242° C.; 1H NMR (DMSO) 12.31 (s, 1 H), 7.88 (d, 2 H, J=8.8 Hz), 7.48 (d, 4 H, J=7.25 Hz), 7.55-7.30 (m, 7 H), 7.23 (d, 2 H, J=8.8 Hz), 7.14 (d, 1 H, J=2.4 Hz), 6.97 (dd, 1 H, J=2.2 Hz, 8.8 Hz), 5.20 (s, 2 H), 5.17 (s, 2 H); MS eI m/z 430 (M+).

Workup

  1. waitAfter this period
  2. waitThe reaction was let go for the additional 1 hr at 0° C. and 2 hrs at rt
  3. customThe progress of the reaction
  4. customthe solid residue purified by trituration with methanol
  5. customto yield (4.0 g, 63.8%)

Sources & evidence

ORD record
ord-487e17edf7e346df9f98d6c6707ad232
Source dataset
uspto-grants-2001_05
Patent number
US06225308B1

Reaction notes

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