1,1'-Carbonyldiimidazole → HCID 46236014, compound

HRID 2069141Notes

Reaction equation

HRID 2069141 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[C:13]([C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[NH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([O:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49]([N:51]3[CH2:55][CH2:54][CH2:53][CH2:52]3)=[O:50])[CH:43]=2)=[CH:33][CH:32]=1>C(Cl)Cl>[C:13]([C:17]1[CH:21]=[C:20]([NH:22][C:6](=[O:7])[NH:30][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:34]([O:41][C:42]3[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49]([N:51]4[CH2:55][CH2:54][CH2:53][CH2:52]4)=[O:50])[CH:43]=3)=[CH:33][CH:32]=2)[N:19]([C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 68229384HCID 68229384, compound

Product 1

HCID 46236014HCID 46236014, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of Intermediate K2 (110 mg, 0.29 mmol) in MeOH (20 mL) containing AcOH (4 drops) was subjected to hydrogenation by passage through a Thales H-cube (1.0 mL min−1, 25° C., 70 mm 10% Pt/C Cat-Cart, full hydrogen mode) and was then evaporated in vacuo. The crude product was partitioned between DCM (20 mL) and aqueous NaHCO3 (10 mL) and the organic layer was washed with brine (10 mL) and evaporated in vacuo to afford N-(4-(4-aminonaphthalen-1-yloxy)pyridin-2-yl)pyrrolidine-1-carboxamide as a brown solid (680 mg, 66%); Rt 1.43 min (Method 2); m/z 349 (M+H)+ (ES+), which was used directly in the next step. To a solution of CDI (100 mg, 0.197 mmol) in dry DCM (1.0 mL) was added 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (85 mg, 0.370 mmol), portionwise, over 20 min and the resulting solution maintained at RT for 16 hr. A portion of this solution (0.6 mL) was added to a solution of N-(4-(4-aminonaphthalen-1-yloxy)pyridin-2-yl)pyrrolidine-1-carboxamide (680 g, 0.255 mmol) in DCM (1.0 mL) and the mixture maintained at RT for 18 hr. The reaction was quenched by the addition of MeOH (2.0 mL) and the resulting mixture was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 4 g, [5% MeOH in DCM] in DCM, 0-100%, gradient elution) to afford the title compound, Example 55, as a yellow brown solid (29 mg, 24%); Rt 5.00 min (Method 1 basic); m/z 604 (M+H)+ (ES+); 1H NMR (400 MHz, DMSO-d6) δ: 1.28 (9H, s), 1.78 (4H, m), 2.39 (3H, s), 3.30 (4H, m, partially obscured by HOD peak), 6.40 (1H, s), 6.60 (1H, dd), 7.30 (1H, d), 7.37 (2H, d), 7.45-7.47 (3H, overlapping m), 7.56 (1H, m), 7.64 (1H, m), 7.84 (1H, d), 7.95 (1H, d), 8.07 (1H, d), 8.09 (1H, d), 8.63 (1H, s), 8.77 (1H, s), 9.10 (1H, s)

Workup

  1. temperaturethe mixture maintained at RT for 18 hr
  2. customThe reaction was quenched by the addition of MeOH (2.0 mL)
  3. customthe resulting mixture was evaporated in vacuo
  4. customThe residue was purified by flash column chromatography (SiO2, 4 g, [5% MeOH in DCM] in DCM, 0-100%, gradient elution)

Sources & evidence

ORD record
ord-912e6665e63d4c27ae397e21968e1b45
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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