Acetic Acid → HCID 58438177, compound

HRID 2092383Notes

Reaction equation

HRID 2092383 reaction equation
[C@H:1]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][C:11](=[O:38])[N:12]([C:23]3[CH:28]=[CH:27][C:26]([N:29]([CH3:37])[CH2:30][CH:31]4[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]4)=[CH:25][CH:24]=3)[CH:13]2[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[CH:8][C:7]=1[O:39][CH3:40])([CH2:3][CH3:4])[CH3:2].[CH3:41]C(O)=O.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C@H:1]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][C:11](=[O:38])[N:12]([C:23]3[CH:28]=[CH:27][C:26]([N:29]([CH3:37])[CH2:30][CH:31]4[CH2:36][CH2:35][CH2:34][N:33]([CH3:41])[CH2:32]4)=[CH:25][CH:24]=3)[CH:13]2[C:16]2[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[CH:8][C:7]=1[O:39][CH3:40])([CH2:3][CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58438004HCID 58438004, compound

Product 1

HCID 58438177HCID 58438177, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Example 45 (TFA salt, 7 mg, 0.01 mmol) in DCM (0.5 ml) were successively added AcOH (0.001 ml, 0.021 mmol), formaldehyde (37% in water, 0.002 ml, 0.021 mmol) and NaBH(OAc)3 (4.4 mg, 0.021 mmol) at RT. The reaction mixture was stirred at RT for 1 h, then diluted into DCM and washed with a 2M aqueous Na2CO3 solution. The organic phase was dried over Na2SO4, filtered and evaporated to dryness. The crude material was purified by reverse phase prep-HPLC (Waters system) to yield the title compound (TFA salt, 7.4 mg, 0.01 mmol, quant.) as a colorless solid. HPLC: AtRet=2.11 min; LC-MS: m/z 576.3 [M+H]+; 1H NMR (500 MHz, DMSO-d6): 0.83-0.92 (2t, J=7.5, 3H, mixture of diastereoisomers), 1.10-1.20 (2d, J=6.1, 3H, mixture of diastereoisomers), 1.44-1.67 (m, 4H), 1.69-1.87 (m, 2H), 2.04-2.19 (m, 1H), 2.65-2.81 (m, 5H), 2.84-2.93 (m, 3H), 3.08-3.19 (m, 1H), 3.22-3.41 (m, 3H), 3.56 (d, J=20.0, 1H), 3.72 (s, 3H), 3.91 (d, J=20.0, 1H), 4.17-4.27 (m, 1H), 5.91-5.96 (m, 1H), 6.58-6.63 (m, 2H), 6.83 (s, 1H), 6.88-6.94 (m, 2H), 6.98-7.02 (m, 1H), 7.32-7.37 (m, 4H).

Workup

  1. customat RT
  2. washwashed with a 2M aqueous Na2CO3 solution
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude material was purified by reverse phase prep-HPLC (Waters system)

Sources & evidence

ORD record
ord-d75bcaa66a2845ad8bf6bc82b312fff3
Source dataset
uspto-grants-2013_05
Patent number
US08440693B2

Reaction notes

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