Dimethylformamide → HCID 86602720, compound

HRID 269736Notes

Reaction equation

HRID 269736 reaction equation
[C:1]([O:4][C@@H:5]1[CH2:9][CH2:8][C@H:7]([CH2:10][C:11]([OH:13])=O)[CH2:6]1)(=[O:3])[CH3:2].CN(C)C=O.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)C(C)C)C.[CH3:34][O:35][C:36]1[C:41]2[N:42]=[C:43]([NH2:45])[S:44][C:40]=2[C:39]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)=[CH:38][CH:37]=1.C(=O)([O-])O.[Na+]>ClCCl>[C:1]([O:4][C@@H:5]1[CH2:9][CH2:8][C@H:7]([CH2:10][C:11]([NH:45][C:43]2[S:44][C:40]3[C:39]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:38][CH:37]=[C:36]([O:35][CH3:34])[C:41]=3[N:42]=2)=[O:13])[CH2:6]1)(=[O:3])[CH3:2]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 114028614-Methoxy-7-morpholinobenzo[d]thiazol-2-amineHCID 69309045[(1S,3R)-3-(Acetyloxy)cyclopentyl]acetic acid

Product 1

HCID 86602720HCID 86602720, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (rac)-(cis)-3-(acetyloxy)-cyclopentaneacetic acid (770 mg, 4.1 mmol) and N,N-dimethylformamide (0.01 ml, 0.13 mmol) in dichloromethane (10 ml) were added oxalyl chloride (1.4 ml, 17 mmol) and the resulting solution stirred for 18 h at ambient temperature. After evaporation of the volatile components in vacuo, the residue was taken up in toluene (10 ml) and again evaporated to dryness. The obtained acid chloride was then dissolved in dichloromethane (20 ml) and subsequently treated with N-ethyl-diisopropyl amine (2.5 ml, 15 mmol) and 4-methoxy-7-morpholin-4-yl-benzothiazol-2-ylamine (960 mg, 3.6 mmol). After stirring for 2 h at ambient temperature and another hour at 50° C., the mixture was cooled to room temperature and treated with saturated aqueous sodium hydrogen carbonate (15 ml) and extracted twice with dichloromethane (20 ml each). After drying over magnesium sulphate and evaporation of the solvents, flash chromatography (silica, eluent dichloromethane/ethyl acetate 85:15) afforded (rac)-(cis)-2-(3-acetoxy-cyclopentyl)-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-acetamide as off-white solid. Separation by preparative chiral HPLC (Chiralpack AD, eluent heptane/isopropanol 85:15) afforded the title compound as first eluting isomer. Light yellow solid (4% yield). MS: m/e=434(M+H+), mp 171-172° C.

Workup

  1. customAfter evaporation of the volatile components in vacuo
  2. customagain evaporated to dryness
  3. dissolutionThe obtained acid chloride was then dissolved in dichloromethane (20 ml)
  4. stirringAfter stirring for 2 h at ambient temperature and another hour at 50° C.
  5. temperaturethe mixture was cooled to room temperature
  6. extractionextracted twice with dichloromethane (20 ml each)
  7. dry with materialAfter drying over magnesium sulphate and evaporation of the solvents, flash chromatography (silica, eluent dichloromethane/ethyl acetate 85:15)

Sources & evidence

ORD record
ord-2b98e2df78ab4ddaba53379d1cd11226
Source dataset
uspto-grants-2008_11
Patent number
US07449461B2

Reaction notes

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