Acetic Acid → HCID 86345339, compound

HRID 60671Notes

Reaction equation

HRID 60671 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:24][C:25]([NH:27][C@@H:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C@H:31]([O:38][C:39]3[CH:40]=[CH:41][C:42]4[N:43]([C:45]([N:48]5[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]5)=[N:46][N:47]=4)[CH:44]=3)[CH2:30][CH2:29]2)=[O:26])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C=O.[C:56](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:24][C:25]([NH:27][C@@H:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C@H:31]([O:38][C:39]3[CH:40]=[CH:41][C:42]4[N:43]([C:45]([N:48]5[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]5)=[N:46][N:47]=4)[CH:44]=3)[CH2:30][CH2:29]2)=[O:26])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([CH3:56])[CH2:20][CH2:19]3)[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86345340HCID 86345340, compound

Product 1

HCID 86345339HCID 86345339, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of Example 68 (605 mg, 0.82 mmol) in DCM (8 mL) was added formaldehyde solution (37 wt % in H2O, 610 μL, 8.19 mmol), followed by acetic acid (47 μL, 0.82 mmol), and then sodium triacetoxyborohydride (347 mg, 1.64 mmol) and the reaction stirred at RT under a N2 atmosphere. After 3 h, the reaction was partitioned between H2O and DCM, and passed through a phase separator cartridge. The organics were concentrated in vacuo and subjected to FCC, eluting with 0-7.5% 2M NH3 in MeOH/DCM, and the product purified further by HPLC (XBridge C18 column, 45-85% MeCN in H2O, 0.1% NH4OH, 20 min gradient, 18 mL/min) to afford the title compound (331 mg, 54%). LCMS (Method 5): Rt 3.61 min, m/z 752, 754 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.58-1.65 (2H, m), 1.65-1.77 (6H, m), 1.80-1.97 (4H, m), 2.11 (3H, s), 2.12-2.23 (4H, m), 3.14 (4H, t, J=5.1 Hz), 4.45-4.55 (1H, m), 4.76-4.83 (1H, m), 5.55 (1H, t, J=4.3 Hz), 6.33 (1H, s), 7.04 (1H, broad d, J=8.4 Hz), 7.08 (1H, dd, J=2.3, 8.6 Hz), 7.15 (1H, dd, J=2.2, 9.7 Hz), 7.22-7.36 (4H, m), 7.36-7.41 (1H, m), 7.52-7.56 (1H, m), 7.59-7.65 (2H, m), 8.13 (1H, s).

Workup

  1. customthe reaction was partitioned between H2O and DCM
  2. concentrationThe organics were concentrated in vacuo
  3. washeluting with 0-7.5% 2M NH3 in MeOH/DCM
  4. customthe product purified further by HPLC (XBridge C18 column, 45-85% MeCN in H2O, 0.1% NH4OH, 20 min gradient, 18 mL/min)

Sources & evidence

ORD record
ord-8aefab84b8b948348d0d6bec78b0152f
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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