Chloroacetyl chloride → HCID 70980697, compound

HRID 1475512Notes

Reaction equation

HRID 1475512 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].Cl[CH2:19][C:20](Cl)=[O:21].[C:23]([O:27][C:28]([N:30]1[CH2:35][C@H:34]([CH2:36][N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[NH:33][CH2:32][C@H:31]1[CH3:43])=[O:29])([CH3:26])([CH3:25])[CH3:24]>C(Cl)Cl.N1C=CC=CC=1>[C:23]([O:27][C:28]([N:30]1[CH2:35][C@H:34]([CH2:36][N:37]2[CH2:38][CH2:39][O:40][CH2:41][CH2:42]2)[N:33]([CH2:19][C:20]([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:21])[CH2:32][C@H:31]1[CH3:43])=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 70980375HCID 70980375, compoundHCID 70982022HCID 70982022, compound

Product 1

HCID 70980697HCID 70980697, compoundYield 12.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (100 mg, 0.42 mmol) in DCM (5 mL) and pyridine (0.5 mL) at 0° C. was treated with chloroacetyl chloride (0.036 mL, 0.46 mmol). After 2 h the solution was treated with (2R,5S)-2-methyl-5-morpholin-4-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester (124 mg, 0.42 mmol) and further pyridine (0.5 mL). After overnight stirring at room temperature no coupling had occurred: the mixture was concentrated in vacuo, diluted with DMF (3 mL), treated with DMAP (1 mg) and heated to 75° C. After 6 h, LC/MS showed ˜80% progression. The mixture was cooled and partitioned between DCM and water. The aqueous phase was extracted with DCM. The combined organic phases were dried (Na2SO4), filtered and concentrated to dryness. Purification by preparative HPLC gave a pale brown glass (30 mg, 12%). MS: [M+H]+=580

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additiondiluted with DMF (3 mL)
  3. additiontreated with DMAP (1 mg)
  4. temperatureheated to 75° C
  5. waitAfter 6 h
  6. temperatureThe mixture was cooled
  7. custompartitioned between DCM and water
  8. extractionThe aqueous phase was extracted with DCM
  9. dry with materialThe combined organic phases were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-a5576869f93d410ca045ad7d2edba899
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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