Chloroacetyl chloride → HCID 86724037, compound

HRID 1475509Notes

Reaction equation

HRID 1475509 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[N:12]=[CH:11][C:10]3[C:13]([CH3:17])([CH3:16])[CH2:14][NH:15][C:9]=3[CH:8]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.ClCC(Cl)=O.[C:34]([O:38][C:39]([N:41]1[CH2:46][C@H:45]([CH2:47][N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[N:44]([CH2:54][C:55](O)=[O:56])[CH2:43][C@H:42]1[CH3:58])=[O:40])([CH3:37])([CH3:36])[CH3:35]>C(Cl)Cl>[C:34]([O:38][C:39]([N:41]1[CH2:46][C@H:45]([CH2:47][N:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)[N:44]([CH2:54][C:55]([N:15]2[C:9]3[CH:8]=[C:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:19][CH:18]=4)[N:12]=[CH:11][C:10]=3[C:13]([CH3:17])([CH3:16])[CH2:14]2)=[O:56])[CH2:43][C@H:42]1[CH3:58])=[O:40])([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 81531Diisopropylethylamine2×HCID 70979857HCID 70979857, compoundHCID 70980400HCID 70980400, compound

Product 1

HCID 86724037HCID 86724037, compoundYield 71.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

To a stirred solution of 6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine (0.11 g, 0.43 mmol) and diisopropylethylamine (0.082 mL, 0.061 g, 0.47 mmol) in DCM (3 mL) at 0° C. under nitrogen was added chloroacetyl chloride (0.036 mL, 0.051 g, 0.45 mmol) and the mixture was stirred at 20° C. for 1 h. Further diisopropylethylamine (0.22 mL, 0.166 g, 1.29 mmol) was added, followed by a solution of (2R,5S)-4-carboxymethyl-2-methyl-5-morpholin-4-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester (0.141 g, 0.47 mmol) in DCM (2 mL). The mixture was stirred at 35° C. for 64 h, then the mixture was partitioned between saturated aqueous NaHCO3 and DCM (×3) and combined organic extracts were dried and evaporated. Chromatography (SiO2, gradient elution with 0-100% EtOAc in 40-60 PE) gave the title compound (0.184 g) as an oil. MS: [M+H]+=596.

Workup

  1. stirringThe mixture was stirred at 35° C. for 64 h
  2. customthe mixture was partitioned between saturated aqueous NaHCO3 and DCM (×3)
  3. customwere dried
  4. customevaporated
  5. washChromatography (SiO2, gradient elution with 0-100% EtOAc in 40-60 PE)

Sources & evidence

ORD record
ord-fd119b8c326c47a2a3d0fc00e4161e1f
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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