Dichloromethane → HCID 24987444, compound

HRID 446879Notes

Reaction equation

HRID 446879 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][S:15]([C:18]1[CH:30]=[CH:29][C:21]([C:22]([NH:24][CH2:25][C:26]([OH:28])=O)=[O:23])=[CH:20][CH:19]=1)(=[O:17])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC([N:38]1[CH2:44][CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)=O)(C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[Cl:76]CCl>CN(C)C=O>[ClH:76].[N:38]1([C:26](=[O:28])[CH2:25][NH:24][C:22](=[O:23])[C:21]2[CH:29]=[CH:30][C:18]([S:15](=[O:16])(=[O:17])[NH:14][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[O:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:19][CH:20]=2)[CH2:44][CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 31475850HCID 31475850, compound

Product 1

HCID 24987444HCID 24987444, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [4-(2-phenoxy-phenylsulfamoyl)-benzoylamino]-acetic acid (Example 2.1/c) (36 mg, 0.085 mmol) in a mixture of dichloromethane (2 mL) and dimethylformamide (0.2 mL) and [1,4]diazepane-1-carboxylic acid tert-butyl ester (Fluka) (20 mg, 0.1 mmol), HBTU (46 mg, 0.12 mmol) and triethylamine (30 μL, 0.2 mmol) were added. The mixture was stirred at room temperature for 24 h, then purified by column chromatography using Kieselgel 60 (0.015-0.040 mm) as adsorbent (Merck) and gradient elution starting with 100% A eluent and processing to 100% B eluent over a period of 20 minutes (eluent A: n-hexane; eluent B: ethyl acetate). The purified compound was dissolved in ethyl acetate (0.5 mL) 2.5 M hydrogen chloride in ethyl acetate (2.0 mL) was added and the mixture was stirred at room temperature for 24 h. The precipitated product was filtered, washed with diethyl ether and dried in vacuum to yield 29 mg (62%) of the title compound. MS (EI) 509.2 (MH+).

Workup

  1. additionwere added
  2. custompurified by column chromatography
  3. washas adsorbent (Merck) and gradient elution
  4. waitprocessing to 100% B eluent over a period of 20 minutes
  5. dissolutionThe purified compound was dissolved in ethyl acetate (0.5 mL) 2.5 M hydrogen chloride in ethyl acetate (2.0 mL)
  6. additionwas added
  7. stirringthe mixture was stirred at room temperature for 24 h
  8. filtrationThe precipitated product was filtered
  9. washwashed with diethyl ether
  10. customdried in vacuum

Sources & evidence

ORD record
ord-8277d7226c334b42a76c1745429837e4
Source dataset
uspto-grants-2013_07
Patent number
US08481527B2

Reaction notes

Loading…