Sodium triacetoxyborohydride → HCID 86759940, compound

HRID 1743323Notes

Reaction equation

HRID 1743323 reaction equation
[NH2:1][CH:2]([C:6]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14](=[O:23])[C:13]2[C:8](=[CH:9][C:10]([Cl:24])=[CH:11][CH:12]=2)[N:7]=1)[CH:3]([CH3:5])[CH3:4].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:39]([NH:46][CH2:47][CH2:48][CH:49]=O)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40].C(OC(=O)NCCCNC(C1N(CC2C=CC=CC=2)C(=O)C2C(=CC(Cl)=CC=2)N=1)C(C)C)(C)(C)C>C(Cl)Cl>[C:42]([O:41][C:39](=[O:40])[N:46]([NH:1][CH:2]([C:6]1[N:15]([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:14](=[O:23])[C:13]2[C:8](=[CH:9][C:10]([Cl:24])=[CH:11][CH:12]=2)[N:7]=1)[CH:3]([CH3:5])[CH3:4])[CH2:47][CH2:48][CH3:49])([CH3:45])([CH3:44])[CH3:43]

Participants

6

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 10910051tert-Butyl N-(3-oxopropyl)carbamateHCID 222387982-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-oneHCID 53473333HCID 53473333, compound

Product 1

HCID 86759940HCID 86759940, compoundYield 110%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath was charged with 10.0 g of 2-(1-amino-2-methyl-propyl)-3-benzyl-7-chloro-3H-quinazolin-4-one (a compound of Formula 301 prepared, e.g., as described in Example 1.6 or 3.1), 50 mL of DCM and 6.20 g (1.2 eq) of sodium triacetoxyborohydride and cooled to 10° C., followed by the portionwise addition of N-Boc-3-aminopropanal 7.1 g (1.4 eq). Upon indication of completion by TLC, the reaction was quenched with 2.0 mL of methanol and stirred for an additional 30 minutes, during which a slight exotherm was observed. The mixture was washed with 1 N hydrochloric acid (until the aqueous layer was clear and acidic)(also exothermic) and then washed with 2N sodium hydroxide (until basic), followed by drying over sodium sulfate, and filtration. The resulting off-white foam solid was filtered and solvents partially stripped under vacuum to give 16.0 g (110% yield) of the title compound of Formula 302, {3-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-propyl}-carbamic acid tert-butyl ester.

Workup

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath
  2. customprepared
  3. customUpon indication of completion by TLC, the reaction was quenched with 2.0 mL of methanol
  4. washThe mixture was washed with 1 N hydrochloric acid (until the aqueous layer
  5. washacidic)(also exothermic) and then washed with 2N sodium hydroxide (until basic)
  6. dry with materialby drying over sodium sulfate, and filtration
  7. filtrationThe resulting off-white foam solid was filtered

Sources & evidence

ORD record
ord-a0b375527af7417bb29a1826763b01e7
Source dataset
uspto-grants-2006_03
Patent number
US07009049B2

Reaction notes

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