Formaldehyde → HCID 70162828, compound

HRID 1018333Notes

Reaction equation

HRID 1018333 reaction equation
[CH2:1]([O:8][C:9](=[O:41])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][C:17]([C:19]2[N:20]=[C:21]([C@@H:36]3[CH2:40][CH2:39][CH2:38][NH:37]3)[NH:22][C:23]=2[CH2:24][CH2:25][C:26]23[CH2:35][CH:30]4[CH2:31][CH:32]([CH2:34][CH:28]([CH2:29]4)[CH2:27]2)[CH2:33]3)=[O:18])[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:44](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:41])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][C:17]([C:19]2[N:20]=[C:21]([C@@H:36]3[CH2:40][CH2:39][CH2:38][N:37]3[CH3:44])[NH:22][C:23]=2[CH2:24][CH2:25][C:26]23[CH2:35][CH:30]4[CH2:29][CH:28]([CH2:34][CH:32]([CH2:31]4)[CH2:33]2)[CH2:27]3)=[O:18])[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69686630HCID 69686630, compound

Product 1

HCID 70162828HCID 70162828, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a rapidly stirred solution of (S)-3-{[5-(2-adamantan-1-yl-ethyl)-2-pyrrolidin-2-yl-1H-imidazole-4-carbonyl]-amino}-benzoic acid benzyl ester (Example 136, step d) (180 mg, 0.33 mmol) and formaldehyde (100 μl, 37% aqueous) in dichloroethane (5 ml) was added sodium triacetoxyborohydride (100 mg, 0.47 mmol). After stirring for 1 h at room temperature the reaction mixture was diluted with DCM and the solution was washed with saturated sodium bicarbonate. The organic layer was dried (MgSO4) and the solvent was evaporated. The residue was purified by flash column chromatography (silica, DCM/hexane/IPA, 9:9:2) to afford the product as a white solid (130 mg, 71%). 1H NMR (300 MHz, CDCl3) 9.70 (1H, br s), 9.12 (1H, s), 8.17 (1H, d), 8.12 (1H, s), 7.77 (1H, d), 7.47-7.35 (6H, m), 5.37 (2H, s), 3.41 (1H, m), 3.20 (1H, m), 3.06 (2H, m), 2.30 (4H, s+m),1.96-1.55 (19H, m), 1.42 (2H, m).

Workup

  1. washthe solution was washed with saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent was evaporated
  4. customThe residue was purified by flash column chromatography (silica, DCM/hexane/IPA, 9:9:2)

Sources & evidence

ORD record
ord-cc2bcd0512d244648f3ed475016154be
Source dataset
uspto-grants-2002_11
Patent number
US06479531B1

Reaction notes

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