Acetic Acid → HCID 85472068, compound

HRID 871091Notes

Reaction equation

HRID 871091 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]5[NH:24][C:25]([CH:27]6[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]6)=[CH:26][C:19]=45)[CH:16]=[CH:17][C:12]=3[N:11]=[CH:10]2)[CH:5]=[N:6][CH:7]=1.FC(F)(F)C([O-])=O.C(N(CC)CC)C.C(O)(=O)C.[OH:51][CH:52]([CH2:55]O)[CH:53]=[O:54].C([BH3-])#N>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]5[NH:24][C:25]([CH:27]6[CH2:32][CH2:31][N:30]([CH2:55][CH:52]([OH:51])[CH2:53][OH:54])[CH2:29][CH2:28]6)=[CH:26][C:19]=45)[CH:16]=[CH:17][C:12]=3[N:11]=[CH:10]2)[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 751GlyceraldehydeHCID 8471TriethylamineHCID 84468TrifluoroacetateHCID 498716Cyano-borohydrideHCID 85472347HCID 85472347, compound

Product 1

HCID 85472068HCID 85472068, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of Example 12D trifluoroacetate salt (60 mg), triethylamine (0.06 mL, 0.422 mmol) and acetic acid (42 mg, 0.703 mmol) in dichloromethane (2 mL) was added 2,3-dihydroxypropanal (25.3 mg, 0.281 mmol) and MP-cyanoborohydride (224 mg, 0.563 mmol) and the mixture was stirred at room temperature for 2 days. The solid was filtered and rinsed with 10 mL 50% methanol/dichloromethane. The filtrate was concentrated and purified by reverse-phase HPLC (Phenomenex Luna C8 AXIA column, 100 Å), eluting with a gradient of 10-95% acetonitrile/0.1% trifluoroacetic acid in water with 10 mM ammonium acetate to afford the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 1.65-1.79 (m, 2 H) 1.91-1.98 (m, 2 H) 2.12-2.25 (m, 2 H) 2.29-2.43 (m, 2 H) 2.65-2.76 (m, 1 H) 2.95-3.05 (m, 2 H) 3.33-3.46 (m, 2 H) 3.60-3.71 (m, 1 H) 5.67 (s, 2 H) 6.11 (s, 1 H) 7.09 (d, J=4.88 Hz, 1 H) 7.57 (dd, J=8.54, 1.53 Hz, 1 H) 7.61-7.68 (m, 1 H) 7.75-7.86 (m, 2 H) 8.15 (d, J=4.88 Hz, 1 H) 8.42 (s, 1 H) 8.46-8.51 (m, 2 H) 11.29 (s, 1 H). MS (ESI) m/e 501 (M+H)+.

Workup

  1. filtrationThe solid was filtered
  2. washrinsed with 10 mL 50% methanol/dichloromethane
  3. concentrationThe filtrate was concentrated
  4. custompurified by reverse-phase HPLC (Phenomenex Luna C8 AXIA column, 100 Å)
  5. washeluting with a gradient of 10-95% acetonitrile/0.1% trifluoroacetic acid in water with 10 mM ammonium acetate

Sources & evidence

ORD record
ord-6f140e4767af4db892bad343c05de021
Source dataset
uspto-grants-2015_03
Patent number
US08969375B2

Reaction notes

Loading…