Ammonia → HCID 57687017, compound

HRID 908434Notes

Reaction equation

HRID 908434 reaction equation
[CH2:1]=O.[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][N:13]([CH:15]3[CH2:19][NH:18][CH:17]([C:20]([NH:22][CH3:23])=[O:21])[CH2:16]3)[CH:14]=2)=[CH:6][C:5]=1[C:24]1[O:25][C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=1.[Na].N>CO.ClCCl>[NH2:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][N:13]([C@H:15]3[CH2:19][N:18]([CH3:1])[C@H:17]([C:20]([NH:22][CH3:23])=[O:21])[CH2:16]3)[CH:14]=2)=[CH:6][C:5]=1[C:24]1[O:25][C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 712FormaldehydeHCID 5360545SodiumHCID 67389059HCID 67389059, compound

Product 1

HCID 57687017HCID 57687017, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

TFA (5 ml) was added to (2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate under argon. The resulting solution was stirred at 25° C. for 1 hour. The solution was evaporated under reduced pressure, adsorbed with ammonia in methanol solution. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) as a pale yellow solid. 37% Aqueous formaldehyde (8.42 μl) at 0° C. was added to a stirred solution 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) dissolved in methanol (2 ml) and dichloromethane (2 ml) over a period of 5 minutes under argon. The resulting solution was stirred at 0° C. for 5 minutes. Sodium triacetoxyhydroborate (23.96 mg, 0.11 mmol) was added and the mixture was stirred 5 minutes at 25° C. A solution of ammonia in methanol 7N (1 ml) was added and the mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N,1-dimethyl-pyrrolidine-2-carboxamide (30 mg) after overnight stirring in acetonitrile as a solid. NMR Spectrum: (DMSOd6) 2.23-2.32 (m, 1H), 2.35 (s, 3H), 2.47-2.56 (m partially hidden by DMSOd5, 1H), 2.65 (d, 3H), 2.76-2.84 (m, 1H), 3.19-3.27 (m, 1H), 3.47-3.56 (m, 1H), 4.89-4.99 (m, 1H), 7.41-7.50 (m, 2H), 7.67 (bs, 2H), 7.77-7.82 (m, 1H), 7.83-7.87 (m, 1H), 7.90 (q, 1H), 7.97 (s, 1H), 8.37 (s, 1H), 8.44 (d, 1H), 8.53 (d, 1H) Mass spectrum: M+H+ 418

Workup

  1. stirringthe mixture was stirred 5 minutes at 25° C
  2. customThe crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane
  3. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-c79cf360d29e420bbae5ea90038e9399
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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