Formaldehyde → HCID 178464484, compound

HRID 1445233Notes

Reaction equation

HRID 1445233 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:32])[CH2:27][NH:28]CCO)[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH:33][C:34]([C:36]2[NH:37][CH:38]=[C:39]([C:41]#[N:42])[N:40]=2)=[O:35])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1.[BH-](OC(C)=O)(OC(C)=O)[O:44][C:45]([CH3:47])=O.[Na+].C=O>CO>[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]1([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:21][CH2:22][N:23]([C:26](=[O:32])[C:27]([CH3:2])([NH2:28])[CH2:47][CH2:45][OH:44])[CH2:24][CH2:25]3)[CH:17]=[CH:16][C:15]=2[NH:33][C:34]([C:36]2[NH:37][CH:38]=[C:39]([C:41]#[N:42])[N:40]=2)=[O:35])[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178510411HCID 178510411, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 178464484HCID 178464484, compoundYield 113.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-{1-[2-(2-hydroxy-ethylamino)-acetyl]-piperidin-4-yl}-phenyl)-amide trifluoroacetic acid salt (as prepared in Example 44, step (c), 50.0 mg, 0.085 mmol) in MeOH (3 mL) was treated with Na(OAc)3BH (39.5 mg, 0.19 mmol) and 37% aqueous formaldehyde (8.2 μL, 0.10 mmol). The mixture was stirred at room temperature for 5.5 h, and the solvents were removed in vacuo. Reverse phase HPLC (C-18 column) (10% to 50% acetonitrile in water with 0.1% TFA over 30 min) afforded the title compound (19.5 mg, 47%) as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.12 (d, 1H, J=8.4 Hz), 8.02 (s, 1H), 7.19 (dd, 1H, J=8.4, 2.0 Hz), 7.09 (d, 1H, J=2.0 Hz), 5.84-5.79 (m, 1H), 4.72-4.64 (m, 1H), 4.39-4.23 (m, 2H), 3.84-3.79 (m, 1H), 3.31-3.21 (m, 1H), 3.03-2.94 (m, 6H), 2.92-2.80 (m, 2H), 2.32-2.24 (m, 4H), 2.00-1.90 (m, 2H), 1.90-1.76 (m, 5H), 1.78-1.59 (m, 2H). LC-MS (ESI, m/z): Calcd. for C27H34N6O3 491.3 (M+H), found 491.2.

Workup

  1. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-c6d259d2afeb4dceb8dc47dee680d58e
Source dataset
uspto-grants-2010_02
Patent number
US07662837B2

Reaction notes

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