Chloroacetyl chloride → HCID 70981733, compound

HRID 1475430Notes

Reaction equation

HRID 1475430 reaction equation
[F:1][C:2]([C:7]1[N:12]=[CH:11][C:10]2[C:13]([CH3:17])([CH3:16])[CH2:14][NH:15][C:9]=2[CH:8]=1)([F:6])[CH2:3][CH2:4][CH3:5].C(N(CC)C(C)C)(C)C.Cl[CH2:28][C:29](Cl)=[O:30].[C:32]([O:36][C:37]([N:39]1[CH2:44][C@H:43]([CH:45]([OH:51])[C:46]2[S:47][CH:48]=[CH:49][N:50]=2)[NH:42][CH2:41][C@H:40]1[CH3:52])=[O:38])([CH3:35])([CH3:34])[CH3:33].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:32]([O:36][C:37]([N:39]1[CH2:44][C@H:43]([CH:45]([OH:51])[C:46]2[S:47][CH:48]=[CH:49][N:50]=2)[N:42]([CH2:28][C:29]([N:15]2[C:9]3[CH:8]=[C:7]([C:2]([F:6])([F:1])[CH2:3][CH2:4][CH3:5])[N:12]=[CH:11][C:10]=3[C:13]([CH3:16])([CH3:17])[CH2:14]2)=[O:30])[CH2:41][C@H:40]1[CH3:52])=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 70980375HCID 70980375, compoundHCID 70981039HCID 70981039, compound

Product 1

HCID 70981733HCID 70981733, compoundYield 21.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (0.252 g, 1.05 mmol) and N,N-diisopropylethylamine (0.28 g, 2.2 mmol) in DCM (4.2 mL) cooled with an ice bath under nitrogen was added chloroacetyl chloride (0.09 g, 0.8 mmol), dropwise. After stirring at this temperature for 1.5 h, (2R,5R)-5-(hydroxy-thiazol-2-yl-methyl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.18 g, 0.6 mmol) in DCM (0.5 mL) was added. The reaction was stirred at room temperature for 18 h, then saturated aqueous sodium bicarbonate was added and the mixture extracted with DCM (3×). The combined organic extracts were filtered and concentrated. Chromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60) gave the title compound (0.076 g). MS: [M+H]+=594.

Workup

  1. stirringThe reaction was stirred at room temperature for 18 h
  2. extractionthe mixture extracted with DCM (3×)
  3. filtrationThe combined organic extracts were filtered
  4. concentrationconcentrated
  5. washChromatography (silica gel, gradient elution, 0-100%, EtOAc in petrol 40-60)

Sources & evidence

ORD record
ord-0981037a3af84f3eaba0d2d9ccefdd72
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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