Cyclopropanecarboxaldehyde → HCID 22676744, compound

HRID 1006268Notes

Reaction equation

HRID 1006268 reaction equation
[CH:1]1([CH:4]=O)[CH2:3][CH2:2]1.[NH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=1)[C:11]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[C:10]2[C:30]1[CH:35]=[CH:34][C:33]([C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:32][CH:31]=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:36]([C:33]1[CH:32]=[CH:31][C:30]([C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([NH:6][CH2:4][CH:1]4[CH2:2][CH2:3]4)[CH:8]=3)[N:12]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[C:11]=2[C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:35][CH:34]=1)([CH3:39])([CH3:37])[CH3:38]

Participants

6

Reactant 3

HCID 123114CyclopropanecarboxaldehydeHCID 4311764Sodium borohydrideHCID 22676732HCID 22676732, compound

Product 1

HCID 22676744HCID 22676744, compoundYield 78.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cyclopropanecarboxaldehyde (168 mg, 2.4 mmol) was added to a stirred mixture of ethyl 5-amino-3-(4-tert-butylphenyl)-1-(3-methoxybenzyl)-1H-indole-2-carboxylate (Example 160, 530 mg, 1.2 mmol) in toluene (12 mL) and molecular sieves (2 g). The reaction was stirred for 16 h and then filtered using toluene to rinse. The filtrate was concentrated in vacuo and the residue was dissolved in methanol (12 mL). Sodium borohydride (15 mg, 1.2 mmol) was added and the reaction was stirred for 2 h. The mixture was diluted with ethyl acetate (50 mL), washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 4:1 hexane/ethyl acetate afforded 480 mg (78%) of desired product. The product had: 1H NMR (300 MHz, acetone-D6) δ 7.45-7.48 (m, 2 H), 7.34-7.38 (m, 2 H), 7.31 (d, 1 H), 7.18 (dd, 1 H), 6.87 (dd, 1H), 6.77 (ddd, 1 H), 6.65-6.70 (m, 2 H), 6.62 (d, 1 H), 5.75 (s, 2 H), 4.68 (s, 1 H), 4.08 (q, 2 H), 3.69 (s, 3 H), 2.89 (d, 2 H), 1.37 (s, 9 H), 1.00-1.10 (m, 1 H), 0.93 (t, 3 H), 0.42-0.49 (m, 2 H), 0.16-0.25 (m, 2 H).

Workup

  1. filtrationfiltered
  2. washto rinse
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutionthe residue was dissolved in methanol (12 mL)
  5. stirringthe reaction was stirred for 2 h
  6. washwashed with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3cc6863955fe480280af80d962ce51ec
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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