1,1-Dichloroethane → HCID 68003642, compound

HRID 1621274Notes

Reaction equation

HRID 1621274 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][N:6]1[C:14]2[C:9](=[C:10]([F:16])[CH:11]=[C:12]([F:15])[CH:13]=2)[C:8]([S:17]([CH2:20][C:21]([OH:23])=O)(=[O:19])=[O:18])=[CH:7]1.[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.C1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.ClC(Cl)C>>[Br:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][CH:26]=1)[CH2:5][N:6]1[C:14]2[C:9](=[C:10]([F:16])[CH:11]=[C:12]([F:15])[CH:13]=2)[C:8]([S:17]([CH2:20][C:21]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[O:23])(=[O:18])=[O:19])=[CH:7]1

Participants

6

Reactant 5

HCID 63651,1-DichloroethaneHCID 104392-AminopyridineHCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 68003667HCID 68003667, compound

Product 1

HCID 68003642HCID 68003642, compound

Procedure

2-((1-(3-bromobenzyl)-4,6-difluoro-1H-indol-3-yl)sulfonyl)acetic acid (30 mg, 0.68 mmol) from Step D, 2-amino-pyridine (13 mg, 0.135 mmol), PyClu (45 mg, 0.135 mmol), and DIEA (29 μL, 0.169 mmol) were added to dichloroethane (3 mL) and microwave irradiated at 110° C. for 30 minutes. The solvent was removed in vacuo and the remaining residue was purified on a Gilson reverse phase HPLC system with a Phenomenex, Luna 50×21.2 mm, 5 uM C18 column (5%-95% water:acetonitrile over 6 min) to yield the desired product. LCMS>99% 215 nm, RT=0.78 min, m/z=520 ([79Br]m+1), 522 ([81Br]m+1). 1H NMR (400 MHz, DMSOD6) 10.89 (s, 1H), 8.47 (s, 1H), 8.41 (d, J=4.0 Hz, 1H), 8.02 (d, J=8.0 Hz, 1H), 7.86 (t, J=8.4 Hz, 1H), 7.66 (s, 1H) 7.59 (d, J=8.4 Hz, 2H), 7.38-7.34 (m, 2H), 5.61 (s, 2H), 4.64 (s, 2H), 2.16 (s, 3H). HRMS found 520.0142; calculated for C22H17N3O3SBrF2, 520.0142.

Workup

  1. customirradiated at 110° C. for 30 minutes
  2. customThe solvent was removed in vacuo
  3. customthe remaining residue was purified on a Gilson reverse phase HPLC system with a Phenomenex, Luna 50×21.2 mm, 5 uM C18 column (5%-95% water:acetonitrile over 6 min)

Sources & evidence

ORD record
ord-a92a04b91a4b4a85b8d3b431bb61c532
Source dataset
uspto-grants-2014_07
Patent number
US08772509B2

Reaction notes

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