Isobutyraldehyde → HCID 57774411, compound

HRID 1695925Notes

Reaction equation

HRID 1695925 reaction equation
[CH3:1][C:2]([CH3:44])([CH3:43])[CH2:3][CH2:4][N:5]1[C:9](=[O:10])[C@H:8]([CH2:11][C:12](=[O:31])[N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)[S:7][CH:6]1[C:32]1[S:36][C:35]([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)=[N:34][CH:33]=1.[CH:45](=O)[CH:46]([CH3:48])[CH3:47].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]([CH3:44])([CH3:43])[CH2:3][CH2:4][N:5]1[C:9](=[O:10])[C@H:8]([CH2:11][C:12](=[O:31])[N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)[S:7][CH:6]1[C:32]1[S:36][C:35]([CH:37]2[CH2:38][CH2:39][N:40]([CH2:45][CH:46]([CH3:48])[CH3:47])[CH2:41][CH2:42]2)=[N:34][CH:33]=1

Participants

5

Reactant 3

HCID 6561IsobutyraldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 57774392HCID 57774392, compound

Product 1

HCID 57774411HCID 57774411, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (5S)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)-2-(2-(piperidin-4-yl)thiazol-5-yl)thiazolidin-4-one (30 mg, 0.04 mmol, 1 eq) in DCM (3 mL) was added isobutyraldehyde (6 mg; 0.08 mmol, 2 eq) and NaBH(OAc)3 (27 mg, 0.12 mmol, 3 eq). The reaction mixture was stirred at RT for 18 h, then quenched with MeOH (0.1 mL) and sat. NaHCO3 (1 mL). The reaction mixture was diluted with DCM (10 mL) and washed with water (5 mL), brine (5 mL), dried (MgSO4) and then concentrated in vacuo. The residue was purified by column chromatography over silica gel eluted with 2 to 10% MeOH in DCM to afford (5S)-3-(3,3-dimethylbutyl)-2-(2-(1-isobutylpiperidin-4-yl)thiazol-5-yl)-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)thiazolidin-4-one (23 mg, 79% yield). (M+1) 695. 1H NMR (CDCl3) δ 7.70 (m, 3H), 6.90 (t, J=7.2 Hz, 1H), 6.70 (d, J=7.5 Hz, 1H), 6.49 (NH, 1H), 5.65 (m, 1H), 4.74 (m, 1H), 4.44 (m, 1H), 3.93 (m, 1H), 3.65 (m, 1H), 3.45-3.35 (m, 3H), 3.17-2.59 (m, 9H), 2.09-1.41 (m, 15H), 1.35 (m, 1H), 1.00-0.85 (m, 15H) ppm.

Workup

  1. customquenched with MeOH (0.1 mL) and sat. NaHCO3 (1 mL)
  2. additionThe reaction mixture was diluted with DCM (10 mL)
  3. washwashed with water (5 mL), brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography over silica gel
  7. washeluted with 2 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-d1c3ebe261fe49979a44b5e221747bf4
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

Loading…