Aluminium lithium hydride → HCID 59394155, compound

HRID 1887636Notes

Reaction equation

HRID 1887636 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9](=O)[CH2:10][N:11]1[CH:20]([CH3:21])[CH2:19][C:18]2[C:17]([O:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[N:28]([C:32](=[O:44])[NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=3)[CH:27]=[CH:26]4)=[N:16][CH:15]=[N:14][C:13]=2[CH2:12]1>C1COCC1>[F:43][C:40]([F:41])([F:42])[C:36]1[CH:35]=[C:34]([NH:33][C:32]([N:28]2[C:29]3[C:25](=[CH:24][C:23]([O:22][C:17]4[C:18]5[CH2:19][CH:20]([CH3:21])[N:11]([CH2:10][CH2:9][OH:8])[CH2:12][C:13]=5[N:14]=[CH:15][N:16]=4)=[CH:31][CH:30]=3)[CH:26]=[CH:27]2)=[O:44])[CH:39]=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 67538379HCID 67538379, compound

Product 1

HCID 59394155HCID 59394155, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiAlH4 (0.46 mL, 1.0 M THF) is added to a solution of {6-methyl-4-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,8-dihydro-6H-pyrido[3,4-d]pyrimidin-7-yl}-acetic acid methyl ester (0.125 g, 0.232 mmol) in THF (5 mL). After 0.5 h the excess LiAlH4 is quenched by the addition of saturated aqueous NH4Cl. Workup is done with saturated aqueous NH4Cl and DCM (25 mL each). The residue is then separated via semi-prep HPLC to give 5-[7-(2-hydroxy-ethyl)-6-methyl-5,6,7,8-tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 512.3 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.42 (s, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.11 (d, J=3.5 Hz, 1H), 8.09 (s, 1H), 7.94 (d, J=8.3 Hz, 1H), 7.57-7.65 (m, 1H), 7.41-7.46 (m, 2H), 7.11 (dd, J=9.0, 2.4 Hz, 1H), 6.72-6.78 (m, 1H), 4.47 (t, J=5.4 Hz, 1H), 3.75 (s, 2H), 3.57 (q, J=6.1 Hz, 2H), 3.12-3.22 (m, 1H), 2.88-3.00 (m, 1H), 2.54-2.76 (m, 3H), 1.10 (d, J=6.6 Hz, 3H).

Workup

  1. customAfter 0.5 h the excess LiAlH4 is quenched by the addition of saturated aqueous NH4Cl
  2. customThe residue is then separated via semi-prep HPLC

Sources & evidence

ORD record
ord-709759638e3f43e1b9bd0d06bfbfb27b
Source dataset
uspto-grants-2013_08
Patent number
US08501756B2

Reaction notes

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