Hydrochloric Acid → 4-(4-Fluoro-phenyl)-2-isopropyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydro-quinazoline

HRID 1917264Notes

Reaction equation

HRID 1917264 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][C:14](=O)[CH2:13][C:12]=3[N:11]=[C:10]([CH:19]([CH3:21])[CH3:20])[N:9]=2)=[CH:4][CH:3]=1.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.[BH3-]C#N.[Na+].Cl>CO.CC1C(Br)=C(O)C(Br)=CC=1C1(C2C=C(Br)C(O)=C(Br)C=2C)OS(=O)(=O)C2C=CC=CC1=2>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][CH2:15][CH:14]([N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:13][C:12]=3[N:11]=[C:10]([CH:19]([CH3:21])[CH3:20])[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 666163744-(4-fluoro-phenyl)-2-isopropyl-5,8-dihydro-6H-quinazolin-7-one

Product 1

HCID 578812824-(4-Fluoro-phenyl)-2-isopropyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydro-quinazoline

Reagents, catalysts & solvents 2

HCID 6451Bromocresol GreenCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of the product of Step F (0.128 g) in MeOH (4 mL) was added of bromocresol green (0.003 g), pyrrolidine (0.06 mL), and NaBH3CN (0.20 g). To this mixture was added 1 M HCl in MeOH until a persistent color change to yellow was observed. After 30 min, the mixture was quenched with 1 M NaOH and poured into water (50 mL). The mixture was extracted with CH2Cl2, dried and concentrated. Chromatography on SiO2 (0 to 5% 2 M NH3 in MeOH/CH2Cl2) afforded 0.015 g of the desired compound. MS (ESI): exact mass calcd. for C21H26FN3, 339.21; m/z found, 340.4 [M+H]+. 1H NMR (CDCl3): 7.59-7.54 (m, 2H), 7.18-7.13 (m, 2H), 3.76-3.68 (m, 1H), 3.50-3.44 (m, 1H), 3.41-3.35 (m, 1H), 3.28-3.14 (m, 2H), 3.0-2.93 (m, 1H), 2.88-2.70 (m, 4H), 2.36-2.23 (m, 3H), 2.19-2.09 (m, 1H), 1.98-1.87 (m, 2H).

Workup

  1. customthe mixture was quenched with 1 M NaOH
  2. additionpoured into water (50 mL)
  3. extractionThe mixture was extracted with CH2Cl2
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f7430ac9bbe9466ba79d96f71407bbfe
Source dataset
uspto-grants-2013_12
Patent number
US08618288B2

Reaction notes

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