Trifluoroacetic acid → HCID 86687777, compound

HRID 1473693Notes

Reaction equation

HRID 1473693 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3OC)[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:32][O:33][CH2:34][C@H:35]1[CH2:39][CH2:38][CH2:37][NH:36]1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O>CN(C=O)C>[CH3:32][O:33][CH2:34][C@H:35]1[CH2:39][CH2:38][CH2:37][N:36]1[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 86687456HCID 86687456, compound

Product 1

HCID 86687777HCID 86687777, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A vial was charged with 4-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (Intermediate KKKK; 0.075 g, 0.157 mmol) and DMF (0.786 ml). (R)-2-(methoxymethyl)pyrrolidine (0.036 ml, 0.314 mmol) was added followed by Hunig's base (0.082 ml, 0.472 mmol). The reaction was stirred for 30 seconds at room temperature. TFA (0.2 ml, 2.60 mmol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered through a frit, concentrated, and purified via Gilson HPLC (5-50% MeCN:H2O w/ 0.1% TFA modifier). The product fractions were passed through an Isolute SCX ion exchange column (pre-wetted with methanol). The column was flushed with methanol, then the product was liberated by flushing the column several times with 2.0 M ammonia in methanol. The product-containing filtrate was concentrated to afford (R)-4-(2-(methoxymethyl)pyrrolidin-1-yl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide as an off-white solid. (ESI) 406.2 (M+H)+.

Workup

  1. stirringthe reaction was stirred overnight at room temperature
  2. filtrationThe reaction was filtered through a frit
  3. concentrationconcentrated
  4. custompurified via Gilson HPLC (5-50% MeCN:H2O w/ 0.1% TFA modifier)
  5. customThe column was flushed with methanol
  6. customby flushing the column several times with 2.0 M ammonia in methanol
  7. concentrationThe product-containing filtrate was concentrated

Sources & evidence

ORD record
ord-aeea286d4d6546f9b2b1684e39675030
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…