Sodium cyanoborohydride → 3-[[2,2-Dimethyl-1,3-dioxolan-4(S)-yl]methyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

HRID 1379867Notes

Reaction equation

HRID 1379867 reaction equation
[NH2:1][C:2]([CH3:20])([CH3:19])[CH2:3][C:4]([NH:6][C@@H:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[NH:9][C:8]1=[O:18])=[O:5].[CH2-:21][C:22]([CH3:24])=[O:23].O=[CH:26][C@@H:27]([CH2:29]O)[OH:28].C([BH3-])#N.[Na+]>CO.C(O)(=O)C.O1CCCC1>[CH3:21][C:22]1([CH3:24])[O:28][C@@H:27]([CH2:29][NH:1][C:2]([CH3:20])([CH3:19])[CH2:3][C:4]([NH:6][C@@H:7]2[CH2:13][CH2:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[NH:9][C:8]2=[O:18])=[O:5])[CH2:26][O:23]1

Participants

7

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 186514543-Amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamideHCID 178521098HCID 178521098, compound

Product 1

HCID 228774543-[[2,2-Dimethyl-1,3-dioxolan-4(S)-yl]methyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamideYield 78%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 368 mg (1.34 mmol) of 3-amino-3-methyl- N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide (Step A) in 10 mL of dry methanol was added 1.5 g of dry 4 Å powdered molecular sieves followed by a solution of 520 mg (4.0 mmol) of D-glyceraldehyde acetonide (used crude as prepared according to the procedure of L. W. Hertel, C. S. Grossman and J. S. Kroin, Syn. Comm. 1991, 21, 151-154.) in 5 mL of dry methanol. The pH of the mixture was carefully adjusted to 6 by the addition of 3 drops of acetic acid. The reaction was stirred for 5 hours at room temperature at which time 4.0 mL (4.0 mmol) of a 1.0 M solution of sodium cyanoborohydride in tetrahydrofuran was added by syringe. The reaction was stirred for 16 hours then filtered through a pad of Celite. The solvent was removed under vacuum to afford a clear oil which was purified by flash column chromatography on silica gel eluting with chloroformB 10% aqueous ammonium hydroxide (33%) in methanol (92:8) to afford 387 mg (78%) of the product as a white solid. 1H NMR (200 MHz, CD3OD): δ 1.10 (s, 6H), 1.28 (s, 3H), 1.34 (s, 3H), 2.08 (m, 1H), 2.26 (dd; 16, 15 Hz; 2H), 2.44 (m, 1H), 2.58-2.75 (m, 3H), 2.87 (m, 1H), 3.63 (dd; 8, 7 Hz; 1H), 4.05 (dd; 8, 7 Hz; 1H), 4.20 (m, 1H), 4.38 (dd; 12, 8 Hz; 1H), 4.84 (s, 1H), 7.00-7.40 (m, 4H). FAB-MS: calculated for C21H31N3O4 389; found 390 (M+H, 100%).

Workup

  1. customas prepared
  2. additionwas added by syringe
  3. filtrationthen filtered through a pad of Celite
  4. customThe solvent was removed under vacuum
  5. customto afford a clear oil which
  6. customwas purified by flash column chromatography on silica gel eluting with chloroformB 10% aqueous ammonium hydroxide (33%) in methanol (92:8)

Sources & evidence

ORD record
ord-fff4564f742144e5ae6b731355d87403
Source dataset
uspto-grants-1997_09
Patent number
US05672596

Reaction notes

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