Formaldehyde → HCID 131726434, compound

HRID 1350151Notes

Reaction equation

HRID 1350151 reaction equation
[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]3[NH:22][CH:21]([CH2:23][CH2:24][CH3:25])[CH2:20][O:19][C:11]3=2)[N:6]=1)([CH3:3])[CH3:2].C=O.[C:28]([BH3-])#N.[Na+]>C(O)(=O)C>[CH:1]([O:4][C:5]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]3[N:22]([CH3:28])[CH:21]([CH2:23][CH2:24][CH3:25])[CH2:20][O:19][C:11]3=2)[N:6]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 21094351HCID 21094351, compound

Product 1

HCID 131726434HCID 131726434, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Compound 117 was prepared according to General Method 5 (EXAMPLE 2) from (±)-3,4-dihydro-8-isopropoxy-3-propyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline (18 mg, 0.05 mmol), 37% aqueous formaldehyde (0.01 mL, 0.3 mmol, 5 eq), sodium cyanoborohydride (16 mg, 0.3 mmol, 5 eq) in 1 mL acetic acid (0.05 M) stirred at rt for 12 h to afford 7 mg of (3R/S)-3,4-dihydro-8-isopropoxy-4-methyl-3-propyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline. This material (7 mg, 0.02 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with 4 mL of a 1:1 acetic acid:concentrated HCl (5 mM) and heated at 90° C. for 6 h to afford 5 mg (83%) of Compound 117 after column chromatography (3:1 hexanes:EtOAc to 1:1 hexanes:EtOAc, gradient elution). 1H NMR (500 MHz, CDCl3) δ 10.83 (bs, 1H), 7.11 (s, 1H), 6.99 (d, J=8.8, 1H), 6.87 (d, J=8.8, 1H), 4.28 (dd, J=10.7, 2.2, 1H), 4.07 (dd, J=10.7, 2.4, 1H), 3.24 (m, 1H), 2.97 (s, 3H), 1.48 (m, 4H), 0.96 (t, J=7.3, 3H).

Sources & evidence

ORD record
ord-7883e139ba494343b6837b831614e76d
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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