Methoxyacetaldehyde → HCID 25174591, compound

HRID 549454Notes

Reaction equation

HRID 549454 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@H:14]1[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]#[N:24])[CH:21]=3)[CH2:16][C:15]1([CH3:26])[CH3:25])=[O:12])=[CH:5]2.[CH3:27][O:28][CH2:29][CH:30]=O>C1COCC1.C(Cl)Cl>[C:23]([C:20]1[CH:21]=[C:22]2[C:17]([CH2:16][C:15]([CH3:26])([CH3:25])[C@H:14]2[NH:13][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([NH:1][CH2:30][CH2:29][O:28][CH3:27])=[CH:10][CH:9]=3)=[O:12])=[CH:18][CH:19]=1)#[N:24]

Participants

4

Reactant 2

HCID 91563MethoxyacetaldehydeHCID 25174434HCID 25174434, compound

Product 1

HCID 25174591HCID 25174591, compoundYield 35.1%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a solution of (R)-5-amino-N-(6-cyano-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)-1H-indole-2-carboxamide (66.0 mg, 0.192 mmol) (prepared as described in Example 9) and methoxyacetaldehyde (containing 13% water, 18.0 mg, 0.211 mmol) in 1:1 THF/CH2Cl2 (4 mL) was added NaB(Oac)3H at rt in one portion. The mixture was stirred at rt for 4 hr and the reaction was quenched with saturated with NaHCO3 solution. The mixture was extracted with ethyl acetate (3×20 mL). The combined extract was washed with brine and dried over anhydrous MgSO4. The desired product (27.1 mg, 35% yield) was isolated as a pale yellow solid by prep. HPLC. LCMS (M+H)+=345.38. 1H NMR (500 MHz, DMSO-d6) δ: 11.1 (s, 1H), 8.34 (d, J=9.3 Hz, 1H, 7.69 (d, J=8.2 Hz, 1H), 7.59 (s, 1H), 7.45 (d, J=7.7 Hz, 1H), 7.17 (d, J=8.8 Hz, 1H), 7.03 (s, 1H), 6.68 (d, J=8.2 Hz, 1H), 6.61 (s, 1H), 5.36 (d, J=9.3 Hz, 1H), 5.00 (t, J=5.8 Hz, 1H), 3.51 (t, J=6.0 Hz, 2H), 3.28 (s, 3H), 3.16 (dt, J=11.5, 6.0 Hz, 2H), 2.86 (dd, J=23.0, 16.5 Hz, 2H), 1.20 (s, 3H), 0.93 (s, 3H).

Workup

  1. customthe reaction was quenched with saturated with NaHCO3 solution
  2. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  3. extractionThe combined extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous MgSO4

Sources & evidence

ORD record
ord-3439170b34864d74bc0c81a1168a92b0
Source dataset
uspto-grants-2011_05
Patent number
US07943658B2

Reaction notes

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