Diethyl Ether → [4-(4-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-pyridin-2-yl]-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester

HRID 912278Notes

Reaction equation

HRID 912278 reaction equation
C[O:2][C:3](=O)[CH2:4][N:5]([C:13]1[CH:18]=[C:17]([N:19]2[C:23]3[N:24]=[C:25]([N:53]4[CH2:58][CH2:57][O:56][CH2:55][CH2:54]4)[N:26]=[C:27]([C:28]4[CH:29]=[N:30][C:31]([N:34]([CH2:44][C:45]5[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=5)[CH2:35][C:36]5[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=5)=[N:32][CH:33]=4)[C:22]=3[CH2:21][CH2:20]2)[CH:16]=[CH:15][N:14]=1)[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].C(OCC)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[C:9]([O:8][C:6](=[O:7])[N:5]([C:13]1[CH:18]=[C:17]([N:19]2[C:23]3[N:24]=[C:25]([N:53]4[CH2:58][CH2:57][O:56][CH2:55][CH2:54]4)[N:26]=[C:27]([C:28]4[CH:29]=[N:30][C:31]([N:34]([CH2:35][C:36]5[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=5)[CH2:44][C:45]5[CH:46]=[CH:47][C:48]([O:51][CH3:52])=[CH:49][CH:50]=5)=[N:32][CH:33]=4)[C:22]=3[CH2:21][CH2:20]2)[CH:16]=[CH:15][N:14]=1)[CH2:4][CH2:3][OH:2])([CH3:12])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 21226445Aluminium lithium hydrideHCID 59244850HCID 59244850, compound

Product 1

HCID 59244826[4-(4-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-pyridin-2-yl]-(2-hydroxy-ethyl)-carbamic acid tert-butyl esterYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A THF solution (5 ml) of {[4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-pyridin-2-yl]-tert-butoxycarbonyl-amino}-acetic acid methyl ester (135 mg, 0.168 mmol) obtained in Step B was cooled to −40°, and 1.0M diethyl ether solution (0.20 ml, 0.20 mmol) of lithium aluminium hydride was added, which was gradually raised to 0° C. over 1 hour. The reaction mixture was quenched with aqueous potassium sodium tartrate solution, followed by extraction with dichloromethane (15 ml×2). The organic layers were combined, and washed with saturated aqueous sodium chloride solution. After the organic layer was dried over magnesium sulfate, the magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane/methanol=50:1), to obtain [4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-pyridin-2-yl]-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester as a yellow solid (73 mg, 56%).

Workup

  1. customThe reaction mixture was quenched with aqueous potassium sodium tartrate solution
  2. extractionfollowed by extraction with dichloromethane (15 ml×2)
  3. washwashed with saturated aqueous sodium chloride solution
  4. dry with materialAfter the organic layer was dried over magnesium sulfate
  5. filtrationthe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-e41e973027ea4f80a73603b4c8feab66
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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