Triethylamine → HCID 21882279, compound

HRID 1977241Notes

Reaction equation

HRID 1977241 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)-1 H-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 o 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, 68.3%). 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, 68.3%)

Sources & evidence

ORD record
ord-c184c434059345a0a31faaeb2aa9dadf
Source dataset
uspto-grants-2001_05
Patent number
US06232307B1

Reaction notes

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