Hydrochloric Acid → HCID 58949460, compound

HRID 1676413Notes

Reaction equation

HRID 1676413 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:25]2[N:40]=[CH:39][CH:38]=[CH:37][C:26]=2[C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[S:17][C:10]=12.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:45](C)=O.[Na+].Cl.C([O-])([O-])=O.[Na+].[Na+]>O.C1COCC1.CO>[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:25]2[N:40]=[CH:39][CH:38]=[CH:37][C:26]=2[C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([CH:18]3[CH2:23][CH2:22][N:21]([CH3:45])[CH2:20][CH2:19]3)[S:17][C:10]=12

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 712FormaldehydeHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 42642627HCID 42642627, compound

Product 1

HCID 58949460HCID 58949460, compoundYield 70.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A round-bottomed flask was charged with 2-(3-fluoro-4-(2-(piperidin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)-N-(4-fluorophenyl)nicotinamide (Example 177, Step D, 47 mg, 0.084 mmol), formaldehyde (7.7 mg, 0.084 mmol) 33% in water and THF (5 mL). The mixture was stirred for 30 minutes and then NaBH(OAc)3 (18 mg, 0.084 mmol) was added. The mixture was stirred for another 30 minutes and then HCl (1N, 1 mL) was added. The acid was neutralized with Na2CO3 and the mixture extracted with EtOAc. The organics were dried over sodium sulfate, filtered and concentrated to get product as a free base. The crude product was diluted in MeOH (2 mL) and HCl (0.1 mL, 4N Dioxane) added. The mixture was concentrated under high vacuum to get product (34 mg, 67%) as a yellow solid. LRMS (esi+) 572 m/z (M+1) detected. 1H NMR (CDCl3, 400 MHz) δ 10.65 (s, 1H), 10.55 (br s, 2H). 9.14 (s, 1H), 8.39 (d, J=6 Hz, 2H), 8.34 (m, 1H), 8.18 (d, J=8 Hz, 1H), 8.03 (d, J=13 Hz, 1H), 7.65 (m, 2H), 7.12 (m, 4H), 6.78 (m, 1H), 6.50 (d, J=5.5 Hz, 1H), 3.36 (m, 2H), 3.13 (m, 1H), 2.81 (m, 2H), 2.26 (m, 4H), 2.05 (s, 3H).

Workup

  1. stirringThe mixture was stirred for another 30 minutes
  2. extractionthe mixture extracted with EtOAc
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto get product as a free base
  7. concentrationThe mixture was concentrated under high vacuum

Sources & evidence

ORD record
ord-5809e5524f6b475fab13b593f589df88
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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