1-(Chloroacetyl)pyrrolidine → HCID 178521328, compound

HRID 525110Notes

Reaction equation

HRID 525110 reaction equation
[C:1]12[C:12]([O:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]3)=[N:11][CH:10]=[N:9][C:8]=1[S:7][C:6]1[CH2:5][CH2:4][CH2:3][C:2]2=1.Cl[CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24]>C(O)C>[N:25]1([C:23](=[O:24])[CH2:22][NH:20][C@H:17]2[CH2:18][CH2:19][C@H:14]([O:13][C:12]3[C:1]4[C:2]5[CH2:3][CH2:4][CH2:5][C:6]=5[S:7][C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:15][CH2:16]2)[CH2:29][CH2:28][CH2:27][CH2:26]1.[O:24]=[C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[CH2:22][N:20]([C@H:17]1[CH2:18][CH2:19][C@H:14]([O:13][C:12]2[C:1]3[C:2]4[CH2:3][CH2:4][CH2:5][C:6]=4[S:7][C:8]=3[N:9]=[CH:10][N:11]=2)[CH2:15][CH2:16]1)[CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24]

Participants

5

Reactant 2

HCID 884401-(Chloroacetyl)pyrrolidineHCID 57520343HCID 57520343, compound

Product 2

HCID 178521328HCID 178521328, compoundHCID 178521333HCID 178521333, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexan-1-amine (140 mg, 0.48 mmol, 1.00 equiv) in ethanol (20 mL) was added 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (72 mg, 0.49 mmol, 1.00 equiv) and KI (80 mg, 1.00 equiv) and the resulting solution was stirred for 8 h at 90° C. in an oil bath. After concentrated in vacuo, the crude product (160 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% HCOOH and CH3CN (6.0% CH3CN up to 52.0% in 14 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired trans-1-(pyrrolidin-1-yl)-2-[(4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexyl)amino]ethan-1-one (14.4 mg) as a off-white solid and trans-2-[[2-oxo-2-(pyrrolidin-1-yl)ethyl](4-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yloxy]cyclohexyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one (32.8 mg) as a off-white solid, respectively.

Workup

  1. concentrationAfter concentrated in vacuo
  2. customthe crude product (160 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  3. waitmobile phase, water with 0.05% HCOOH and CH3CN (6.0% CH3CN up to 52.0% in 14 min)
  4. customThe product-containing fractions were collected
  5. custompartially evaporated
  6. customto remove water and CH3CN under reduced pressure
  7. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-7a3eb892ed524db8818827cdc2e8953d
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

Loading…