1-Methyl-1H-indole-3-carbaldehyde → HCID 67071752, compound

HRID 874247Notes

Reaction equation

HRID 874247 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:22])/[CH:5]=[CH:6]/[C:7]1[CH:8]=[C:9]2[C:18](=[CH:19][CH:20]=1)[O:17][C:12]1([CH2:16][CH2:15][NH:14][CH2:13]1)[CH2:11][C:10]2=[O:21].[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([CH:33]=O)=[CH:25]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C([O-])([O-])=O.[Na+].[Na+]>[CH3:2][O:3][C:4](=[O:22])/[CH:5]=[CH:6]/[C:7]1[CH:8]=[C:9]2[C:18](=[CH:19][CH:20]=1)[O:17][C:12]1([CH2:16][CH2:15][N:14]([CH2:33][C:26]3[C:27]4[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:24]([CH3:23])[CH:25]=3)[CH2:13]1)[CH2:11][C:10]2=[O:21]

Participants

5

Reactant 3

HCID 878941-Methyl-1H-indole-3-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67071652HCID 67071652, compound2×

Product 1

HCID 67071752HCID 67071752, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent

Procedure

A suspension of (±)-(E)-3-[4-oxo-spiro(chromane-2,3′-pyrrolidine)-6-yl]acrylic acid methyl ester (284 mg, 0.88 mmol, Intermediate 1) in 1 M Na2CO3, was stirred for 10 min, then extracted with DCM and treated with N-methyl-indol-3-carbaldehyde (167 mg, 1.06 mmol) and NaBH(OAc)3 (297 mg, 1.32 mmol) following the procedure described in Example 2, step A, giving (±)-(E)-3-[1′(1-methyl-1H-indol-3-ylmethyl)-4-oxo-spiro(chromane-2,3′-pyrrolidine)-6-yl]-acrylic acid methyl ester (191 mg, 0.44 mmol, 42%) as a white solid. The resulting ester was hydrolyzed as described in Example 2, step B, giving (±)-(E)-3-[1′(1-methyl-1H-indol-3-ylmethyl)-4-oxo-spiro(chromane-2,3′-pyrrolidine)-6-yl]-acrylic acid (51 mg, 0.11 mmol, 25%) as an orange solid (hydrochloride salt). The product was suspended in DCM (3 ml), TEA (0.025 ml, 0.31 mmol) was added, and the clear solution was treated with NH2OTHP following the procedure described in Example 2, step C, giving (E)-3-[1′(1-methyl-1H-indol-3-ylmethyl)-4-oxo-spiro(chromane-2,3′-pyrrolidine)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (53 mg, 0.10 mmol, 91%) as a light yellow solid. The compound was then dissolved in DCM (3 ml) and treated with 1 M HCl in diethyl ether (3 ml) as described in Example 2, step D, giving a light brown solid after aqueous workup and column chromatography (eluent: DCM/MeOH 9:1) (10 mg, 22%, free base)

Workup

  1. extractionextracted with DCM

Sources & evidence

ORD record
ord-6a63b11984cd4ad3b32172ac0a762e09
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

Loading…