Acetic Acid → HCID 59513610, compound

HRID 1159814Notes

Reaction equation

HRID 1159814 reaction equation
[OH:1][CH2:2][C:3]1[N:4]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:5]2[CH:6]=[C:7]([C:14]([F:17])([F:16])[F:15])[CH:8]=[C:9]([CH:12]=O)[C:10]=2[CH:11]=1.OCC1N(S(C2C=CC=CC=2)(=O)=O)C2C(C=1)=C(C(F)(F)F)C=C(C=O)C=2.C([N:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)(OC(C)(C)C)=O.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[C:21]1([S:18]([N:4]2[C:5]3[C:10](=[C:9]([CH2:12][N:60]4[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]4)[CH:8]=[C:7]([C:14]([F:17])([F:15])[F:16])[CH:6]=3)[CH:11]=[C:3]2[CH2:2][OH:1])(=[O:20])=[O:19])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 86618253HCID 86618253, compoundHCID 86618254HCID 86618254, compound2×

Product 1

HCID 59513610HCID 59513610, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(Hydroxymethyl)-1-(phenylsulfonyl)-6-(trifluoromethyl)-1H-indole-4-carbaldehyde and 2-(Hydroxymethyl)-1-(phenylsulfonyl)-4-(trifluoromethyl)-1H-indole-6-carbaldehyde (Intermediates 71) in dry THF (8 mL), was distributed into two micro wave vials (47 mg, 0.12 mmol, in each), where after 1-BOC-piperazine (46 mg, 0.25 mmol), acetic acid (70 μL, 1.23 mmol) and NaB(OAc)3H (78 mg, 0.37 mmol) were added to each vial. The mixtures were irradiated with microwaves for 720 s at 130° C., filtered and concentrated. The residues were dissolved in MeOH (1.5 mL) and conc. HCl (0.5 mL) and irradiated using microwaves at 100° C. for 300 s, filtered and purified using preparative HPLC/UV (System A, 20-50% MeCN, 0.1% TFA). Concentration of fractions from the compound with shortest retention time gave 38 mg of [1-(phenylsulfonyl)-4-(piperazin-1-ylmethyl)-6-(trifluoromethyl)-1H-indol-2-yl]methanol. Purification was performed by preparative HPLC/UV (System A, 20-50% MeCN, 0.1% NH4OAc). Concentration was followed by extraction using DCM (×2) and aq. Na2CO3/brine. The organic layers were combined, dried, filtered and concentrated to give 7 mg, 6% of a light yellow solid. HPLC purity 98% RT=1.59 min (System A, 10-97% MeCN over 3 minutes), 98% RT=1.35 min (System B, 10-97% MeCN over 3 minutes). 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 2.37 (s, 4 H) 2.88 (t, J=4.71 Hz, 4 H) 3.60 (s, 2 H) 4.95 (s, 2 H) 6.82 (s, 1 H) 7.45 (t, J=7.85 Hz, 2 H) 7.49 (s, 1 H) 7.56 (t, J=7.54 Hz, 1 H) 7.85 (d, J=8.48 Hz, 2 H) 8.19 (s, 1H). 13C NMR (126 MHz, CHLOROFORM-D) δ ppm 45.97 (s, 2 C) 54.23 (s, 2 C) 58.43 (s, 1 C) 63.31 (s, 1 C) 109.04 (s, 1 C) 117.93 (s, 1 C) 121.88-127.09 (m, 1 C) 122.09 (s, 1 C) 124.91 (s, 2 C) 126.55 (s, 2 C) 129.49 (s, 2 C) 134.32 (s, 1 C) 135.61 (s, 1 C) 137.53 (s, 1 C) 138.15 (s, 1 C) 141.98 (s, 1 C). COSY, HSQC and HMBC were also run to confirm the structure. MS (ESI+) for C21H22F3N3O3S m/z 454 (M+H)+

Workup

  1. customThe mixtures were irradiated with microwaves for 720 s at 130° C.
  2. filtrationfiltered
  3. concentrationconcentrated
  4. dissolutionThe residues were dissolved in MeOH (1.5 mL)
  5. customconc. HCl (0.5 mL) and irradiated
  6. customat 100° C.
  7. customfor 300 s
  8. filtrationfiltered
  9. custompurified

Sources & evidence

ORD record
ord-4af86adda6664ca6b9e4bbf089261645
Source dataset
uspto-grants-2010_10
Patent number
US07812017B2

Reaction notes

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