(Diethylamino)sulfur trifluoride → HCID 68350418, compound

HRID 877832Notes

Reaction equation

HRID 877832 reaction equation
CCN(S(F)(F)[F:7])CC.[Br:10][C:11]1[CH:12]=[C:13]2[C:18]([NH:19][C@@H:20]3[CH2:24][N:23]([C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[CH2:22][C@:21]3(O)[CH3:35])=[C:17]([C:37]#[N:38])[CH:16]=[N:15][N:14]2[CH:39]=1>ClCCl>[Br:10][C:11]1[CH:12]=[C:13]2[C:18]([NH:19][C@@H:20]3[CH2:24][N:23]([C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[CH2:22][C@@:21]3([F:7])[CH3:35])=[C:17]([C:37]#[N:38])[CH:16]=[N:15][N:14]2[CH:39]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 86707909HCID 86707909, compound

Product 1

HCID 68350418HCID 68350418, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DAST (0.697 mL, 5.27 mmol) was added to a solution of (3R,4R)-benzyl 4-((6-bromo-3-cyanopyrrolo[1,2-b]pyridazin-4-yl)amino)-3-hydroxy-3-methylpyrrolidine-1-carboxylate (310 mg, 0.659 mmol) in dichloromethane (10 mL) at 0° C. After 5 min at 0° C., the mixture was carefully quenched with saturated NaHCO3 (5 mL), diluted with dichloromethane (80 mL), washed with water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography, eluting with 0 to 30% ethyl acetate in hexanes, to give (3S,4R)-benzyl 4-((6-bromo-3-cyanopyrrolo[1,2-b]pyridazin-4-yl)amino)-3-fluoro-3-methylpyrrolidine-1-carboxylate (120 mg, 39% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.84 (s, 1H), 7.69 (s, 1H), 7.48-7.31 (m, 5H), 6.77 (d, J=8.8 Hz, 1H), 5.25-5.06 (m, 2H), 4.91-4.70 (m, 1H), 4.37-4.21 (m, 1H), 3.99-3.82 (m, 1H), 3.69-3.35 (m, 2H), 1.73-1.55 (m, 3H); MS (ES+) m/z: 472.2 (M+H).

Workup

  1. customthe mixture was carefully quenched with saturated NaHCO3 (5 mL)
  2. additiondiluted with dichloromethane (80 mL)
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 0 to 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c32ba4515ea84f9b88749c5330b9fd0b
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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